Objective To explore the effect of glycolic acid combined with CO2 fractional laser in the treatment of depressed scar after acne. Methods A total of 70 patients with depressed scar after acne admitted to our hospital from February 2023 to February 2024 were selected as the research objects. They were randomly divided into control group and study group, with 35 patients in each group. The control group was treated with CO2 fractional laser, and the study group was treated with glycolic acid combined with CO2 fractional laser. The incidence of adverse reactions, therapeutic effect and GAGS score were compared between the two groups. Results The total effective rate of treatment in the study group was 97.14%, which was higher than 80.00% in the control group (P <0.05). After treatment, the GAGS score of the study group was lower than that of the control group (P <0.05). The incidence of adverse reactions in the study group was 5.71%, which was lower than 22.86% in the control group (P <0.05). Conclusion The effect of glycolic acid combined with CO2 fractional laser in the treatment of depressed scar after acne is good, which can avoid rash, skin redness and swelling, pigmentation and so on, and reduce the symptoms of depressed scar after acne.