To analyze the clinical effect of laser combined with pimecrolimus cream and tacrolimus ointment in the treatment of vitiligo. Methods A total of 82 patients with vitiligo admitted to the Department of Dermatology, Beijing Jingcheng Skin Hospital from June to December 2022 were selected as the research objects. They were divided into conventional group and combined group by random number table method, with 41 patients in each group. The conventional group was treated with laser therapy, and the combined group was treated with pimecrolimus cream and tacrolimus ointment on the basis of laser therapy. The clinical efficacy, immune function, symptom improvement and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the combined group was 97.56%, which was higher than 82.93% in the conventional group, and the difference was statistically significant (P <0.05). After treatment, the levels of IgA, IgM and IgG in the combined group were higher than those in the conventional group, the differences were statistically significant (P <0.05). After treatment, the number of white spots in the combined group was less than that in the conventional group, and the area of white spots was less than that in the conventional group, the differences were statistically significant (P <0.05). The incidence of adverse reactions in the combined group was 7.32%, which was lower than 29.27% in the conventional group, the difference was statistically significant (P <0.05). Conclusion Laser combined with pimecrolimus cream and tacrolimus ointment can improve the therapeutic effect for vitiligo patients, improve their immune function, reduce the number and area of leukoplakia, and reduce the incidence of adverse reactions, which is worthy of clinical application.