Abstract: To investigate anti-aging mechanism of giant salamander bioactive peptides, label-free quantitative (LFQ) proteomics was used after high-abundant proteins were removed. The results of LFQ showed 425 low-abundant proteins in serum in mice, in which 26 proteins were differentially expressed (P<0.05), and covered 14 biological processes, 6 molecular functions and 7 cellular components. Tetrahydrofolate synthase and glycogen phosphorylase were up-regulated expressed significantly (P<0.05), increased by 1.78 times and 1.05 times respectively, while xanthine dehydrogenase was down-regulated expressed significantly (P<0.05) decreased. The expression of these enzymes increased or decreased, which could reduce the amount of free radicals in vivo. In summary, the giant salamander bioactive peptides prevented aging by scavenging free radicals, this study would provide basic data for the use of the giant salamander bioactive peptides.