Objective To investigate the efficacy and safety of tanshinone combined with compound Huangbai liquid and licorzine in the treatment of adolescent acne. Methods A total of 66 adolescent acne patients admitted to Huai'an Maternal and Child Health Care Center from January 2019 to December 2023 were selected as the research subjects. According to different treatment plans, they were divided into group A, group B, and group C, with 22 patients in each group. Group A was treated with compound Huangbai liquid, group B was treated with tanshinone combined with compound Huangbai liquid, and group C was treated with tanshinone combined with compound Huangbai liquid and licorzine. The clinical efficacy, adverse reactions, skin lesion symptoms and quality of life were compared among the three groups. Results The total effective rate in group C (100.00%) was higher than that in group B (77.27%) and group A (54.55%) (P <0.05). There was no significant difference in the total effective rate between group B and group A (P >0.05). The incidence of adverse reactions in group C was lower than that in group B and group A (P <0.05). There was no significant difference in the incidence of adverse reactions between group B and group A (P >0.05). After treatment, the scores of skin lesion symptoms in group C were lower than those in group B and group A (P <0.05). After treatment, the scores of various aspects of quality of life in group C were higher than those in group B and group A (P <0.05). Conclusion The application of tanshinone combined with compound Huangbai liquid and licorzine in the treatment of adolescent acne is effective. It can play a synergistic effect, effectively improve the skin lesion symptoms of patients, and has a low risk of adverse reactions after treatment, which is conducive to improving the quality of life of patients. The application efficacy and safety are high.