Objective To analyze the effect of low-dose isotretinoin combined with compound glycyrrhizin on serum inffammatory factor levels in patients with severe acne. Methods A total of 100 patients with severe acne admitted to the Department of Dermatology of our hospital from January 2023 to December 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 50 patients in each group. The control group was treated with low-dose isotretinoin, and the observation group was treated with compound glycyrrhizin on the basis of the control group. The clinical efffcacy, serum inffammatory factor levels and Global Acne Grading System (GAGS) score were compared between the two groups. Results The total effective rate of treatment in the observation group was higher than that in the control group (P<0.05). After treatment, the levels of TNF-α, IL-8 and IL-6 in the observation group were lower than those in the control group (P<0.05). After treatment, the GAGS score of the observation group was lower than that of the control group (P<0.05). Conclusion The application of low-dose isotretinoin combined with compound glycyrrhizin in the treatment of patients with severe acne can improve clinical efffcacy, effectively reduce serum inffammatory factor levels, and alleviate systemic inffammatory response.