Objective To investigate the efficacy of traditional Chinese medicine (TCM) prescriptions combined with external therapy in the treatment of moderate to severe acne. Methods According to the random number table method, 60 patients with moderate to severe acne admitted to our hospital from January 2025 to August 2025 were divided into a control group (30 cases, conventional treatment) and a study group (30 cases, receiving TCM prescriptions combined with external therapy in addition to the control group). The therapeutic effects of the two groups were compared. Results Before treatment and after 8 weeks of treatment, the water content of the stratum corneum and the skin oil index in both groups increased, with the study group showing higher values than the control group. The transepidermal water loss in both groups decreased, with the study group showing lower values than the control group (P<0.05). The total effective rate of the study group was higher than that of the control group (P<0.05). Before treatment and after 8 weeks of treatment, the scores of the acne grading system (GAGS) in both groups decreased, with the study group showing lower values than the control group (P<0.05). Conclusion The combination of TCM prescriptions and external therapy can significantly improve the skin physiological indicators in patients with moderate to severe acne, enhance therapeutic efficacy, and alleviate skin lesion symptoms.