The synergistic inhibition ratio of glabridin and oxyresveratrol to tyrosinase was optimized by in vitro tyrosinase inhibition experiments and response surface method. The micelle solution of glabridin and oxyresveratrol was prepared according to the optimum activity ratio, and the model mice with chloasma was replicated by medium-wave ultraviolet irradiationUVB radiation. After the micelle solution treatment, the superoxide dismutase and malondialdehyde in the serum and skin tissues of the mice were detected. The results showed that the optimal ratio of glabridin and oxyresveratrol was predicted to be 0.012∶0.020 (mol/L∶mol/L). Glabridin micelle solution,oxyresveratrol micelle solution and glabridin oxyresveratrol compound micelle solution all reduced lipid peroxidation in skin tissue and serum of mice with chloasma, and increased superoxide dismutase activity, compared with model group, superoxide dismutase activity in serum of glabridin oxyresveratrol compound group increased by 24.71 U/mL, malondialdehyde content decreased by 7.90 U/mL; superoxide dismutase activity in skin tissue increased by 15.14 U/mgprot, malondialdehyde content decreased by 1.60 U/mgprot, show thatand glabridin oxyresveratrol compound micelle solution had the best effect. Glabridin and oxyresveratrol have protective effect on the formation of chloasma, and the two have synergistic effect which works better when combined.