Objective To explore the effect of glycolic acid peeling combined with drug therapy on adolescents with moderate-to-severe acne and its influence on aesthetic satisfaction. Methods A total of 180 adolescents with moderate-to-severe acne admitted to our hospital from January 2022 to January 2025 were selected as the research subjects, and they were divided into the control group and the observation group by the random number table method, with 90 adolescents in each group. The control group received drug therapy, and the observation group received glycolic acid peeling combined with drug therapy. The clinical efficacy, scar condition, aesthetic satisfaction, adverse reaction rate and recurrence rate were compared between the two groups. Results The total effective rate of treatment in the observation group (97.78%) was higher than that in the control group (90.00%) (P <0.05). After treatment, the VSS score of the observation group was lower than that of the control group, and the aesthetic satisfaction rate was higher than that of the control group (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P >0.05). The recurrence rate of acne in the observation group was lower than that in the control group (P <0.05). Conclusion Glycolic acid peeling combined with drug therapy has a good effect in the treatment of moderate-to-severe acne in adolescents. It can reduce scar residue, improve skin aesthetics, and has a low risk of adverse reactions and short-term acne recurrence, which is worthy of clinical application.