Objective To explore the green synthesis process of cyclodipeptides and investigate their activity in delaying skin aging. Methods Firstly, three active cyclodipeptides were synthesized by green and mild synthesis technology and analyzed by mass spectrometry. Secondly, the MTT assay and Griess reagent method were used to detect its biotoxicity and anti-inflammatory activity, respectively. Subsequently, the cell-protective effects were assessed by verifying cell proliferation and elastin production. Finally, the antioxidant and anti-aging effects were evaluated by DPPH assay and X-Gal experiments. Results The positive ion peaks of the three cyclodipeptides (CHP, CGY, CSY) detected by mass spectrometry were 235.418, 251.225 and 221.145, respectively, which were consistent with their corresponding molecular weights. There was no difference in cell viability between all concentrations and the control group (P >0.05), and the survival rate was still over 97% at the highest concentration (10 mmol/L), indicating no obvious toxicity. The cyclodipeptides promoted the proliferation of HaCaT cells at all tested concentrations, with significant effects compared to the untreated group (P <0.05). The content of NO production decreased with the increasing concentrations of cyclodipeptides, and its inhibition rate showed a significant increasing trend (P <0.05). Meanwhile, compared with vitamin E, the hydroxyl radicals and negative oxygen anions of the three cyclodipeptides were higher. Compared with the ultravioletirradiated control group, the three cyclodipeptides reduced the production of the blue substrate (P <0.05). Conclusion The three cyclodipeptides not only have high biosafety and biocompatibility, but also have the ability of skin protection and anti-aging, which provides a reference for the research and development of skin aging treatment products.