Abstract: In order to get antioxidative peptides, two commercial enzymes, flavorase and papain were used to hydrolyse Meretrix Meretrix Linnaeus. protein. Based on the results of single factor experiments, liquid-solid ratio, hydrolysis temperature and pH were chosed as influence factors. Box-Benhnken Design Center combination method of three factors and three levels experimental design was applied to further optimize hydrolysis conditions and the degree of hydrolysis (DH) was assayed by Response Surface Methodology. The results showed that: the optimum conditions were 4 h reaction time, enzyme dosage was 3.0% (the ratio of flavorase and papain proteases was 2:1), liquid-solid ratio of 3.25:1, temperature of 51℃，and pH 6.9. Under the optimized conditions, the degree of hydrolysis was 36.11%. The hydrolysates showed obvious in vitro antioxidant activity. The values of IC50 of DPPH radical and hydroxyl radical were 2.61 mg/mL and 3.47 mg/mL, respectively. Thus, the optimized conditions could be used for antioxidative peptides preparation.