Objective To analyze the effect of combined red and blue light therapy on skin barrier function in patients with moderate to severe acne. Methods A total of 80 patients with moderate to severe acne admitted to the Department of Dermatology, Guangzhou Nansha Public Health Clinical Center from January 2024 to December 2025 were selected, and they were divided into the control group and the observation group according to different treatment methods, with 40 patients in each group. The control group was treated with clarithromycin sustained-release tablets plus topical fusidic acid cream, and the observation group was treated with combined red and blue light therapy on the basis of the control group. The clinical efffcacy, lesion severity, skin barrier function, psychological status, adverse reaction rate and recurrence rate were compared between the two groups. Results The total effective rate of the observation group (95.00%) was higher than that of the control group (77.50%) (P<0.05). The GAGS score of the observation group after treatment was better than that of the control group (P<0.05). The skin moisture content, sebum secretion and TEWL in the observation group were better than those in the control group (P<0.05). The scores of GAD-7 and PHQ-9 in the observation group after treatment were lower than those of the control group (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). The recurrence rate of the observation group was lower than that of the control group (P<0.05). Conclusion Combined red and blue light therapy achieves favorable clinical efffcacy in the treatment of moderate to severe acne, which is helpful to rapidly eliminate skin lesions, repair skin barrier, and relieve negative emotions, with high safety and a lower recurrence rate.