To explore the application effect of health education combined with psychological guidance in patients with vitiligo. Methods A total of 50 patients with vitiligo admitted to Maternal and Child Health and Family Planning Service Center of Chengduo County from January 2020 to December 2022 were selected as the research objects. According to different intervention schemes, they were divided into control group and study group, with 25 patients in each group. The control group was given routine nursing, and the study group was given health education and psychological guidance on the basis of the control group. The psychological status, compliance behavior, quality of life and nursing satisfaction were compared between the two groups. Results The scores of HAMD and HAMA in the study group were lower than those in the control group after intervention, and the differences were statistically significant (P <0.05). The proportion of medication, reasonable diet, treatment and emotional control in the study group was higher than that in the control group, and the difference was statistically significant (P <0.05). After intervention, the scores of symptoms, interpersonal relationship, daily activities, work and learning, and feelings in the study group were lower than those in the control group, and the differences were statistically significant (P <0.05). The nursing satisfaction of the study group was 96.00%, which was higher than 76.00% of the control group, and the difference was statistically significant (P <0.05). Conclusion The implementation of health education combined with psychological guidance for patients with vitiligo can effectively improve the negative emotions of patients, improve the compliance behavior and satisfaction of patients, improve the quality of life, and have positive significance for promoting the recovery of the disease.