Objective To analyze the effect of Xiaoyao powder combined with Qibai powder in the treatment of female chloasma with liver depression and qi stagnation. Methods A total of 80 female patients with chloasma of liver depression and qi stagnation type admitted to Xintai Hospital of Traditional Chinese Medicine from January 2022 to July 2023 were selected as the research objects. They randomly were divided into reference group and experimental group, with 40 patients in each group. The reference group was treated with conventional glycolic acid peels liquid, and the experimental group was treated with Xiaoyao powder combined with Qibai powder. The clinical efficacy, facial related indexes and incidence of adverse reactions were compared between the two groups. Results The total effective rate of treatment in the experimental group was 97.50%, which was higher than 80.00% in the reference group, and the difference was statistically significant (P <0.05). After treatment, the scores of TCM syndromes, skin lesion area and stain color in the two groups were lower than those before treatment, and those in the experimental group were lower than those in the reference group, the differences were statistically significant (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion In the treatment of female chloasma patients with liver depression and qi stagnation, the effect of Xiaoyao powder combined with Qibai powder is ideal, which can improve the TCM syndrome score, skin lesion area and color spot color of patients, with high safety and high clinical application value.