Abstract: In this study, collagen was extracted from Phascolosoma esculenta. The hydrolysis conditions for preparing the collagen antioxidant peptides of Phascolosoma esculenta was optimized by single factor test and response surface methodology with the total antioxidant capacity and superoxide anion clearance rate as inspection indicators. In the enzyme screening test, papain, neutral protease, pepsin and acid protease, which obtained polypeptides with higher antioxidant activity were selected for single and compound enzymatic hydrolysis tests. As a result, the compound enzyme hydrolysis of papain and neutral protease was determined as the best solution. On the basis of single factor test results, the compound enzyme addition amount (U/g), enzymatic hydrolysis temperature (℃), enzymatic hydrolysis pH, enzymatic hydrolysis time (h) were determined as independent variables. According to response surface analysis combining with actual factors, the optimal enzymatic hydrolysis conditions were determined as follows: Compound enzyme addition amount was 8135 U/g, enzymatic hydrolysis temperature was 51.6 ℃, enzymatic hydrolysis pH was 6.4, enzymatic hydrolysis time was 4.2 h. Under these conditions, the total antioxidant capacity of the collagen peptide was (1.333±0.021) μmol/mL, and the superoxide anion clearance rate was 78.75%±0.94%.