To investigate the effect of 308 nm excimer laser combined with Babuqi light guide gel in the treatment of vitiligo patients. Methods A total of 110 patients with vitiligo admitted to Zhengzhou Xijing Vitiligo Hospital from August 2021 to April 2023 were selected as the research objects. According to the random number table method, they were divided into the reference group and the study group, with 55 patients in each group. The reference group was treated with 308 nm excimer laser, and the study group was treated with babuqi light guide gel on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared. Results The total effective rate of treatment in the study group was 92.73%, which was higher than 69.09% in the reference group, and the difference was statistically significant (P <0.05). The incidence of adverse reactions in the study group was 3.64%, which was lower than 20.00% in the reference group, the difference was statistically significant (P <0.05). Conclusion The effect of 308 nm excimer laser combined with Babuqi light guide gel in the treatment of vitiligo patients is more ideal, and the safety is higher , which is worthy of clinical application.