Objective To investigate the efficacy of glycolic acid combined with minocycline hydrochloride in the treatment of acne vulgaris. Methods A total of 70 patients with acne vulgaris admitted to our hospital from June 2020 to June 2022 were selected as the research objects. They were divided into control group and observation group by number table method, with 35 patients in each group. The control group was treated with glycolic acid, and the observation group was treated with glycolic acid combined with minocycline hydrochloride. The clinical efficacy, skin oil content, stratum corneum water content and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 97.14%, which was higher than 82.86% in the control group (P<0.05). After treatment, the skin oil content of the observation group was lower than that of the control group, and the water content of the stratum corneum was higher than that of the control group (P<0.05). The incidence of adverse reactions in the observation group was 2.86%, which was lower than 17.14% in the control group (P<0.05). Conclusion Glycolic acid combined with minocycline hydrochloride has a good effect in the treatment of acne vulgaris, which can improve the clinical symptoms, with lesser adverse reactions and higher safety