To explore the application effect of isotretinoin combined with red and blue light therapy in patients with moderate to severe acne. Methods A total of 60 patients with moderate to severe acne admitted to Zunyi Honghuagang District People's Hospital from September 2021 to March 2023 were selected as the research objects. According to the random number table method, they were divided into control group and observation group, with 30 patients in each group. The control group was treated with isotretinoin, and the observation group was treated with isotretinoin combined with red and blue light. The improvement of symptoms, clinical efficacy and adverse reactions were compared between the two groups. Results The improvement of symptoms in the two groups after treatment was better than that before treatment, and the observation group was better than the control group (P <0.05). The total effective rate of treatment in the observation group was 96.67%, which was higher than 80.00% in the control group (P <0.05). The incidence of adverse reactions in the observation group was 10.00%, which was lower than 13.33% in the control group, but the difference was not statistically significant (P >0.05). Conclusion The treatment of moderate to severe acne patients with isotretinoin combined with red and blue light can further improve the treatment efficiency, improve the clinical symptoms of patients, and the treatment safety is also high, which is worthy of clinical application.