Objective To analyze the effect of compound acid combined with compound polymyxin B ointment and doxycycline hyclate tablets on the number of skin lesions in patients with moderate acne. Methods A total of 60 patients with moderate acne admitted to Siyang County First People's Hospital from October 2023 to October 2024 were selected, and they were divided into the control group and the study group by the random number table method, with 30 patients in each group. The control group was treated with compound polymyxin B ointment and doxycycline hyclate tablets, and the study group was treated with compound acid on the basis of the control group. The number of skin lesions, clinical efficacy, drug effect onset time, skin appearance improvement and adverse reaction rate were compared between the two groups. Results The number of skin lesions in the study group was less than that in the control group at the 4th and 8th weeks of treatment (P <0.05). The total effective rate of treatment in the study group was 100.00%, which was higher than 80.00% in the control group (P <0.05). The onset time of drug effect in the study group was shorter than that in the control group (P <0.05). The GAIS scores of the study group at the 4th and 8th weeks of treatment were higher than those of the control group (P <0.05). There were no obvious adverse reactions in the two groups, and no abnormal liver and kidney function and allergic reactions were observed. Conclusion The combination of compound acid with compound polymyxin B ointment and doxycycline hyclate tablets in the treatment of moderate acne can effectively reduce the number of skin lesions, improve skin appearance, with mild and controllable adverse reactions, thus effectively improving clinical effect, which is worthy of clinical application.