Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials

Introduction Skin aging manifests as wrinkles, reduced elasticity, and roughness due to intrinsic and extrinsic factors. Peptide-based therapies enhance collagen synthesis and extracellular matrix integrity. This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of oral and topical peptides in improving hydration, elasticity, wrinkles, and brightness. Methods A comprehensive search of MEDLINE, CENTRAL, and Web of Science was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) assessing peptide effects on skin aging parameters were included. The Cochrane Risk of Bias Tool (RoB 2) assessed study quality. Data were synthesized using a random-effects model in RStudio (R version 4.1.1). Conclusion Nineteen RCTs involving 1,341 participants were analyzed. Peptides, particularly oral formulations, significantly improved hydration and brightness, with a modest pooled effect on wrinkle reduction (MD = 0.27, p = 0.04). Subgroup analysis indicated that this benefit was largely driven by oral polypeptides (MD = 1.5, p = 0.01). While effects on elasticity and density were inconsistent, peptides were well tolerated, with minimal adverse events reported across trials. Overall, peptides appear to be safe, non-invasive anti-aging agents, though larger RCTs with standardized outcomes and histopathologic assessment are warranted. Systematic review registration identifier CRD420250652779.