Objective To investigate the effect isotretinoin soft capsules combined with compound Muniziqi granules on Skin Aesthetics in the treatment of moderate to severe acne. Methods A total of 72 patients with moderate to severe acne admitted to Yixing People’s Hospital from January to December 2023 were selected as the research subjects, and they were divided into control group and observation group by the random number table method, with 36 patients in each group. The control group was treated with isotretinoin soft capsules, and the observation group was treated with compound Muniziqi granules on the basis of the control group. The clinical efficacy, skin lesion counting, skin aesthetics and quality of life were compared between the two groups. Results The total effective rate of treatment in the observation group was 97.22%, which was higher than 80.56% in the control group (P <0.05). After treatment, the number of papules in the two groups was less than that before treatment, and that in the observation group was less than that in the control group (P <0.05). After treatment, the scores of inflammatory lesions and VSS 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 score of quality of life in the observation group was higher than that in the control group (P <0.05). Conclusion The administration of isotretinoin soft capsules+compound Muniziqi granules can improve the skin condition of moderate to severe acne patients, promote their quality of life, and increase the treatment efficacy.