Objective To investigate the effect of salicylic acid antibacterial gel combined with doxycycline and Runzao Zhiyang capsules on skin lesions and sebum secretion in patients with moderate to severe acne. Methods A total of 98 patients with moderate to severe acne admitted to the Department of Dermatology of our hospital from January to December 2025 were selected, and they were divided into the control group and the observation group by the random number table method, with 49 patients in each group. The control group was treated with doxycycline combined with Runzao Zhiyang capsules, and the observation group was treated with topical salicylic acid antibacterial gel on the basis of the control group. The clinical efficacy, skin lesion count, acne severity (IGA score), sebum secretion level, pruritus degree (NRS score) and adverse reactions were compared between the two groups. Results The total effective rate of the observation group was 87.76%, which was higher than 71.43% of the control group (P <0.05). After 4 and 8 weeks of treatment, the counts of inflammatory and noninflammatory lesions in the observation group were less than those in the control group (P <0.05). After 4 and 8 weeks of treatment, the IGA score, sebum secretion level and NRS score of the observation group were lower than those of the control group (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion For patients with moderate to severe acne, salicylic acid antibacterial gel combined with doxycycline and Runzao Zhiyang capsules can improve clinical efficacy, reduce the skin lesion count, and ameliorate sebum secretion and pruritus symptoms, with favorable safety profile.