Objective To explore the clinical effect of adapalene gel combined with doxycycline in the treatment of acne. Methods A total of 86 acne patients admitted to Jianhu County Center for Disease Control and Prevention from January 2021 to December 2023 were selected and randomly divided into control group and observation group, with 43 patients in each group. The control group was treated with doxycycline, and the observation group was treated with doxycycline combined with adapalene gel. The clinical effect, skin lesion count, skin physiological indexes, immune function and inflammatory factor levels were compared between the two groups. Results The total effective rate of the observation group was 95.35%, which was higher than 81.40% of the control group (P<0.05). After treatment, the skin lesion count, skin surface pH value, skin oil content, CD8+, TNF-α, IL-6 and IL-8 in the observation group were lower than those in the control group, and the skin stratum corneum hydration, CD3+, CD4+and CD4+/CD8+ were higher than those in the control group (P<0.05). Conclusion The effect of adapalene gel combined with doxycycline in the treatment of acne patients is precise, which can improve skin lesion status, restore skin physiological indexes, regulate patients' immunity, and reduce the inflammatory response.