Objective To analyze the clinical effect of intense pulsed light combined with mesotherapy and non-ablative laser in the treatment of melasma. Methods A total of 44 melasma patients admitted to Wangcang People's Hospital from September to December 2024 were selected as the research subjects. According to different treatment methods, they were divided into the control group and the study group, with 22 patients in each group. The control group received intense pulsed light combined with mesotherapy, and the study group received intense pulsed light combined with mesotherapy and non-ablative laser. The clinical efficacy, pigmentation and GAIS score were compared between the two groups. Results The total effective rate of treatment in the study group (95.45%) was higher than that in the control group (77.27%) (P <0.05). At 28 days after treatment, the skin melanin index of the study group was lower than that of the control group, and the GAIS score was higher than that of the control group (P <0.05). Conclusion Intense pulsed light combined with mesotherapy and non-ablative laser has a good effect in the treatment of melasma, which can improve the skin melanin index and enhance the overall facial aesthetics. It is worthy of clinical application.