Objective To explore the effect of oral doxycycline hyclate capsules combined with compound huangbai topical solution wet compress on skin lesion improvement in patients with mild to moderate acne. Methods A total of 160 patients with mild to moderate acne admitted to the Department of Dermatology, Inner Mongolia Autonomous Region Maternal and Child Health Care Hospital from January 2023 to June 2024 were selected as the research subjects. According to the random number table method, they were divided into the control group and the observation group, with 80 patients in each group. The control group was treated with oral doxycycline hyclate capsules alone, and the observation group was treated with oral doxycycline hyclate capsules combined with compound Huangbai topical solution wet compress. The clinical efffcacy, skin lesion improvement, skin barrier function improvement, inffammatory factor levels and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group (95.00%) was higher than that in the control group (81.25%) (P<0.05). At the 3rd and 6th weeks of treatment, the inffammatory skin lesion number and non-inffammatory skin lesion number as well as the total skin lesion score in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P<0.05). After treatment, the TEWL, sebum content and stratum corneum hydration in the two groups were better than those before treatment, and those in the observation group were better than those in the control group (P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P<0.05). The incidence of adverse reactions in the observation group (6.25%) was lower than that in the control group (7.50%), but the difference was not statistically signiffcant (P>0.05). Conclusion Compound Huangbai topical solution combined with doxycycline hyclate has a deffnite clinical effect in the treatment of mild to moderate acne. It can effectively reduce the number of skin lesions and inffammatory response, improve skin barrier function, and will not increase the risk of adverse reactions, which is worthy of clinical application.