Abstract: To explore the extraction process and in vitro antioxidant activity of polyphenol and flavonoids, papain was used to enzymatically hydrolyze moutan cortex powder to extract paeonol and flavonoids. The yield of polyphenol, flavonoids and the scavenging rate of DPPH free radicals(DPPH·) were selected as the indexes to optimize the extraction conditions by response surface methodology. Though analysing the established model which verified reliably, the optimal extrating conditions were obtained when the three indexes reached the maximum level separately and simultaneously. The results showed that the optimal extraction process parameters of polyphenol yield were papain 400 U/g, liquid to material ratio 21:1(mL: g), pH 5.5, and enzymatic hydrolysis time 119 min with the yield of polyphenol was 28.96 mg/g. The optimal extraction process parameters of flavonoid yield were papain 400 U/g, liquid to material ratio 20:1(mL: g), pH 6.0, enzymatic hydrolysis time 121 min, with theyield of flavonoids was 44.32 mg/g.The optimal extraction process parameters of DPPH· scavenging rate were papain 400 U/g, liquid to material ratio 21:1(mL: g), pH 6, and enzymatic hydrolysis time 123 min with DPPH· scavenging rate was 66.87%. The optimal extraction process parameter of the yield of polyphenol, flavonoid yield and DPPH· scavenging rate was papain 400 U/g, the ratio of liquid to material 21:1(mL: g), pH 6, and the enzymatic hydrolysis time 122 min with the yield of polyphenol was 28.25 mg/g, the yield of flavonoid was 42.96 mg/g and the DPPH· scavenging rate was 66.72%. The obtained model was reliable, and the prediction of the yield of polyphenol and flavonoids and the scavenging rate of DPPH· was accurate.