Objective To explore the effect of asiaticoside ointment combined with 0.1% tretinoin cream on mMASI score and pigmentation in young and middle-aged female patients with facial melasma. Methods A total of 50 young and middle-aged female patients with facial melasma admitted to Renhe Hospital of Baoshan District from January 2024 to December 2025 were selected as the research subjects. According to the random number table method, they were divided into the control group and the observation group, with 25 patients in each group. The control group was treated with 0.1% tretinoin cream, and the observation group was treated with asiaticoside ointment on the basis of the control group. The modified Melasma Area and Severity Index (mMASI) score, pigmentation, clinical efficacy and adverse reaction rate were compared between the two groups. Results After 12 weeks of treatment, the mMASI score of the observation group was lower than that of the control group (P <0.05). After 12 weeks of treatment, the ΔMI value in the observation group was lower than that in the control group (P <0.05). The total effective rate of the observation group (92.00%) was higher than that of the control group (68.00%) (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion Asiaticoside ointment combined with 0.1% tretinoin cream can effectively alleviate pigmentation in young and middle-aged female patients with facial melasma, reduce mMASI score, and improve clinical efficacy. The combined therapy does not obviously increase adverse reactions and presents favorable safety.