To compare the application effect of phototherapy and immunoregulation in the treatment of vitiligo. Methods A total of 130 patients with vitiligo admitted to Shouguang Skin Disease Prevention and Treatment Station from October 2021 to October 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 65 patients in each group. The control group was treated with immunomodulatory therapy, and the observation group was treated with phototherapy. The clinical efficacy and adverse reactions of the two groups were compared. Results The total effective rate in the observation group was 95.38%, which was higher than 86.15% in the control group, and the difference was statistically significant (P <0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, the difference was statistically significant (P <0.05). Conclusion Both phototherapy and immunomodulation can achieve the purpose of treatment for vitiligo, but phototherapy has better effect and lower risk of adverse reactions, which is worthy of clinical application.