What benefits do peptides offer for the skin?

The peptides are short chains of amino acids that play a key role in cellular communication and skin regeneration. They are particularly popular for preventing skin aging and smoothing wrinkles. Indeed, certain specific peptides, called signal peptides or matrix peptides, directly stimulate the production of collagen, of elastin, of glycosaminoglycans and fibronectin within the extracellular matrix. By reinforcing this structure, the skin gains firmness and elasticity, and wrinkles and fine lines are reduced.

Among these peptides are palmitoyl tripeptide-1 (pal-GHK) and palmitoyl pentapeptide-4 (pal-KTTKS), which function as messengers to fibroblasts, the cells responsible for the synthesis of collagen, elastin, and glycosaminoglycans. Other peptides, such as palmitoyl tripeptide-3/5, mimic extracellular matrix proteins and both stimulate collagen production and inhibit its degradation, thereby reinforcing the skin’s overall structural integrity.

There are also peptides targeting muscle relaxation, known as neurotransmitter-inhibiting peptides, such as acetylhexapeptide-3 (Argireline) or pentapeptide-18, which act on the contraction of the muscles responsible for expression lines. By modulating acetylcholine release at the nerve terminals, these peptides reduce the intensity of muscle contractions, leading to a gradual smoothing of dynamic wrinkles, without the invasive effects of treatments like botox.

The efficacy of peptides in reducing wrinkles is not based solely on mechanistic hypotheses: several clinical studies have confirmed their visible effects on the skin. Among these, a recent study investigated tetrapeptide-68, a peptide derived from loricrin, a protein of the skin barrier. Conducted over 12 weeks in a double-blind design, the study included 25 participants who applied a cream containing 100 ppm of tetrapeptide-68 twice daily. Researchers monitored various skin physiological parameters measuring wrinkle roughness, depth, and density. The results showed a significant decrease in all these parameters, with a progressive improvement from the fourth week and a maximal effect at 12 weeks.

Antioxidant peptides represent a new generation of active ingredients that can strengthen the skin’s natural defenses against free radicals. Some, such as carnosine, glutathione, or anserine, occur naturally in the body or in certain foods, but the majority of antioxidant peptides used in cosmetics are derived from enzymatic hydrolysis or fermentation of plant and animal proteins. These processes yield short chains of amino acids capable of neutralizing free radicals, chelating heavy metals (such as iron and copper), and limiting lipid peroxidation within cell membranes.

Antioxidant peptide efficacy is closely linked to their molecular structure, particularly their size and amino acid composition. Peptides rich in hydrophobic residues such as leucine, alanine, or proline, or in aromatic amino acids like tryptophan, phenylalanine, or histidine, exhibit an enhanced capacity to donate electrons or hydrogen atoms to free radicals. Histidine, in particular, functions via its imidazole ring, which participates in electron and hydrogen transfer reactions. Peptides of low molecular weight (< 1 kDa) also stand out for their improved skin penetration and greater mobility in biological environments, thereby optimizing their antioxidant activity.

How do antioxidant peptides benefit the skin?

By neutralizing free radicals and reinforcing enzymatic defense systems, antioxidant peptides act as a shield against oxidative stress. They prevent membrane lipid peroxidation, collagen fragmentation, and elastin degradation, thus maintaining skin firmness and elasticity. Their ability to chelate pro-oxidant metals such as iron or copper also limits the formation of reactive hydroxyl radicals. In parallel, activation of the Nrf2–ARE pathway stimulates the natural production of protective enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, enhancing cellular resistance to UV rays and pollution.

Antioxidant peptides help maintain smooth, radiant skin and protect it against signs of aging.

The wound healing is a highly orchestrated process involving inflammation, cell migration, fibroblast proliferation, and extracellular matrix reconstruction. Several peptides, notably antimicrobial peptides such as clavanin A or LL-37, have demonstrated interesting pro-regenerative activity on skin cells. In addition to their anti-infective role, these peptides exert an immunomodulatory action that balances pro- and anti-inflammatory responses, thereby promoting an environment conducive to tissue repair.

Studies on human fibroblasts have shown that these peptides stimulate cell proliferation and migration by activating the transcription of certain genes, such as KI67 (cell proliferation) and CXCR4 (a receptor involved in cell migration). These mechanisms are accompanied by an accelerated reconstruction of the dermal tissue, with increased production of collagen, elastin, and proteoglycans necessary for restoring skin structure. Other peptides, such as hBD-2, hBD-3, Crotalus adamanteus toxin-II, or PR-39, also enhance wound healing by stimulating the FGFR1/JAK2/STAT3 signaling pathway, known to promote angiogenesis and fibroblast activation.

An experimental study in a mouse model revealed the strong wound-healing potential of the RL-QN15 peptide. Mice with dorsal wounds received twice-daily topical applications of RL-QN15 at various concentrations, compared to a control group and a positive control (Kangfuxin, known for its healing effect). After only 7 days of treatment, wounds treated with 50 nM of RL-QN15 showed a near-complete regeneration (≈ 100%), significantly higher than that of the control group, which achieved only about 60% healing. The peptide’s efficacy proved dose-dependent, with activity comparable to Kangfuxin but at a concentration roughly 5 million times lower, underscoring its potency. Histological analyses confirmed a rapid, orderly reconstruction of the epidermis and dermis, accompanied by the formation of finer granulation tissue, indicative of higher-quality healing and a reduced risk of fibrosis.

Proper hydration is essential for maintaining the barrier function of the skin, which acts as a true protective interface between the body and the external environment. The hydrolipid film, the intercellular lipids of the stratum corneum and the natural moisturizing factors are key elements of this barrier. When it is well hydrated, the skin retains its suppleness, resilience, and regenerative capacity. Conversely, skin dehydration disrupts cellular cohesion in the stratum corneum, increases transepidermal water loss, and promotes irritation and premature aging.

Certain biomimetic peptides are notable for their moisturizing properties. A 30-day clinical trial assessed the hydrating effects of a hydrogel enriched with biomimetic peptides (SH-Oligopeptide-2, SH-Polypeptide-1, SH-Oligopeptide-1, SH-Polypeptide-42) on the skin of 20 women. The results showed a significant improvement in skin hydration from the first application, compared to untreated skin and a placebo (gel without peptides). These effects were accompanied by a significant enhancement of skin elasticity and radiance, confirming the multifunctional role of peptides.

Peptides are also valued for their anti-inflammatory properties, particularly beneficial for sensitive skin, frequently prone to redness and discomfort. Among these, acetyl dipeptide-1 cetyl ester can be mentioned, which acts directly on the POMC (pro-opiomelanocortin) gene pathway, leading to the production of peptides such as α-MSH that help modulate inflammation. Studies have also shown that it stimulates the expression of genes essential to barrier function, including AQP3, filaggrin, caspase-14, and keratin-10, while reducing prostaglandin E2 production, a mediator of skin hypersensitivity reactions. These combined effects allow the skin to better withstand external aggressors.

Other peptides, such as palmitoyl tripeptide-8, also demonstrate proven soothing effects. Palmitoyl tripeptide-8, inspired by α-MSH, inhibits interleukin-8 production, a pro-inflammatory cytokine. A study conducted on 13 volunteers evaluated its calming effect after skin irritation induced by a 0.5% solution of sodium lauryl sulfate (SDS), known to induce localized inflammation and redness. After 24 hours of exposure to SDS, participants applied a formula containing 4 × 10⁻⁶ M palmitoyl tripeptide-8 or a placebo, three times per day for two days. Thermographic measurements showed that the SDS-induced increase in skin temperature was reduced by an average of 78% in the peptide-treated area, while no significant improvement was observed with the placebo. Video microscopy observations confirmed a visible reduction in redness and inflammation after applying palmitoyl tripeptide-8, illustrating its soothing and anti-inflammatory power on irritated skin.

Thanks to their antibacterial and anti-inflammatory properties, certain peptides are considered promising allies in combating skin imperfections. Moreover, unlike conventional antibiotics, these molecules do not target a single bacterial mechanism involved in acne pathogenesis but instead directly disrupt its cell membrane, making it more difficult for resistance to develop. A recent study highlighted the potential of peptide P156, a derivative of phage lysin Prevotella intermedia (PlyPi01), to target the bacteria Cutibacterium acnes and Staphylococcus aureus, which are associated with inflammatory flare-ups of acne.

Although these results are promising, caution is warranted in their interpretation. The observed antibacterial effects have been demonstrated only in vitro, under controlled laboratory conditions, and have not yet been confirmed by clinical studies on human skin. Furthermore, even though these molecules effectively target acne-related bacteria, they exhibit neither keratolytic action nor mattifying properties, two essential aspects in the comprehensive management of blemishes. Thus, the antibacterial peptides will likely need to be combined with other active ingredients to provide a complete approach to the various mechanisms of acne.

• SCHAGEN S. K. Topical peptide treatments with effective anti-aging results. Cosmetics (2016).

• LOING E. Reaching a zen-like state in skin: Biomimetic peptide to balance sensitivity. Cosmetics and Toiletries (2017).

• MARASCO D. & al. Peptides as therapeutic agents for inflammatory-related diseases. International Journal of Molecular Sciences (2018).

• ALUKO R. E. & al. Structural and functional properties of food protein-derived antioxidant peptides. Journal of Food Biochemistry (2019).

• ALMEIDA I. F. & al. Trending anti-aging peptides. Cosmetics (2020).

• LIU H. & al. Antioxidant activity and inhibition of ultraviolet radiation-induced skin damage of Selenium-rich peptide fraction from selenium-rich yeast protein hydrolysate. Bioorganic Chemistry (2020).

• CARATI D. & al. Application of synthetic peptides to improve parameters of skin physiology: An open observational 30-day study. Journal of Cosmetics, Dermatological Sciences and Applications (2020).

• CLEMENS L. E. & al. Designed antimicrobial peptides for topical treatment of antibiotic resistant acne vulgaris. Antibiotics (2020).

• YANG X. & al. Discovery of a novel short peptide with efficacy in accelerating the healing of skin wounds. Pharmacological Research (2021).

• ALMEIDA I. F. & al. Usage of synthetic peptides in cosmetics for sensitive skin. Pharmaceuticals (2021).

• KANG H. & al. Wrinkle reduction using tetrapeptide-68 contained in an O/W formulation: A randomized double-blind placebo-controlled study. Pharmaceutics (2024).

• LOTT CARVALHO J. & al. Screening of the skin-regenerative potential of antimicrobial peptides: Clavanin A, clavanin-MO, and mastoparan-MO. International Journal of Molecular Sciences (2024).

• ZHAO Y. & al. Novel antioxidant peptides from hydrolyzed proteins of Volvariella volvacea: Purification, characterization and protective effects on H2O2-induced human skin fibroblasts. Food Bioscience (2025).

• LI X. & al. Systematic evaluation and identification of anti-inflammatory and anti-aging ginseng peptides for skincare applications. Cosmetics (2025).

• FISCHETTI V. A. & al. Engineered lysin-derived peptide as a potent antimicrobial for acne vulgaris Antibiotics (2025).