Objective To analyze the effect of compound glycyrrhizin tablets combined with acitretin capsules in the treatment of moderate and severe acne patients and its effect on sex hormones and skin aesthetics. Methods A total of 64 patients with moderate to severe acne admitted to our hospital from January 2022 to December 2023 were randomly divided into control group and observation group, with 32 patients in each group. The control group was treated with acitretin capsules, and the observation group was treated with compound glycyrrhizin tablets combined with acitretin capsules. The clinical efficacy, sex hormone levels and aesthetic satisfaction were compared between the two groups. Results The total effective rate of treatment in the observation group was 81.25%, which was higher than 56.25% in the control group (P <0.05). After treatment, the levels of T, P, E2 and LH in the observation group were better than those in the control group (P <0.05). After treatment, the score of skin aesthetics in the observation group was higher than that in the control group (P <0.05). Conclusion Compound glycyrrhizin tablets combined with acitretin capsules have a good effect in the treatment of moderate to severe acne, which can effectively improve the sex hormone level and acne symptoms, and is conducive to improving skin aesthetics.