Objective To explore the effect of compound cortex phellodendri liquid paint combined with benzoyl peroxide gel in the treatment of patients with mild to moderate acne on their skin lesion symptoms. Methods A total of 56 patients with mild to moderate acne admitted to Jiangxia District Zhifang Street Community Health Service Center from June 2022 to June 2024 were selected as the research subjects. According to the random number table method, they were divided into the reference group and the observation group, with 28 patients in each group. The reference group was treated with benzoyl peroxide gel, and the observation group was treated with compound cortex phellodendri liquid paint combined with benzoyl peroxide gel. The skin lesion symptoms, treatment effect, inflammatory factor levels and quality of life were compared between the two groups. Results After treatment, the scores of various skin lesion symptoms in the observation group were all lower than those in the reference group (P <0.05). The total effective rate of treatment in the observation group (92.86%) was higher than that in the reference group (71.43%) (P <0.05). After treatment, the levels of IL-4, IL-17 and TNF-α in the observation group were all lower than those in the reference group (P <0.05). After treatment, the scores of various quality of life in the observation group were all higher than those in the reference group (P <0.05). Conclusion The application of compound cortex phellodendri liquid paint combined with benzoyl peroxide gel in the treatment of patients with mild to moderate acne has a good effect. It can effectively improve the skin lesion symptoms, alleviate the inflammatory reaction, and is beneficial to improving the quality of life of patients, which is worthy of clinical application.