Objective To analyze the clinical effect of picosecond laser combined with topical tranexamic acid in the treatment of chloasma. Methods Thirty patients with chloasma admitted to Guangzhou Women and Children's Medical Center Liuzhou Hospital from October 2022 to April 2023 were randomly divided into observation group and control group, with 15 patients in each group. The observation group was treated with picosecond laser combined with tranexamic acid, and the control group was treated with tranexamic acid. The clinical efficacy, chloasma area and severity, mood state, treatment satisfaction and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 93.33%, which was higher than 73.33% in the control group, and the difference was statistically significant (P <0.05). The treatment satisfaction of the observation group was 93.33%, which was higher than 80.00% of the control group, and the difference was statistically significant (P <0.05). After treatment, the scores of MASI and POMS in the observation group were lower than those in the control group, and 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 chloasma, picosecond laser combined with tranexamic acid can effectively improve the clinical treatment effect. Compared with single drug treatment, it can improve the symptoms and mood state of chloasma. Meanwhile, the patient's satisfaction with the treatment of chloasma is higher, and it will not increase adverse reactions.