Objective To explore the effect of crisaborole combined with mometasone furoate cream and ultraviolet irradiation on melanogenesis indicators in patients with progressive vitiligo vulgaris. Methods A total of 70 patients with progressive vitiligo vulgaris admitted to Danyang Maternal and Child Health Care Hospital from January 2023 to August 2025 were selected as the research subjects, and they were divided into the control group and the study group by the random number table method, with 35 patients in each group. The control group was treated with mometasone furoate cream combined with ultraviolet irradiation, and the study group was treated with crisaborole on the basis of the control group. The melanogenesis indicators, peripheral blood T cell subset levels, skin lesions and recurrence rate were compared between the two groups. Results After 12 weeks of treatment, the level of ICAM-1 in the study group was lower than that in the control group, and the level of α-MSH was higher than that in the control group (P<0.05). After 12 weeks of treatment, the percentages of CD3+ and CD4+ cells and the CD4+ /CD8+ ratio in the study group were higher than those in the control group, while the percentage of CD8+ cells was lower than that in the control group (P<0.05). After 12 weeks of treatment, the skin lesion area in the study group was smaller than that of the control group, and the skin lesion pigmentation score was higher than that in the control group (P<0.05). The recurrence rate of the study group was lower than that of the control group (P<0.05). Conclusion Crisaborole combined with mometasone furoate cream and ultraviolet irradiation in the treatment of adult progressive vitiligo vulgaris can effectively regulate peripheral blood immune function, promote melanogenesis, reduce disease recurrence rate, and improve patients' skin lesion status.