Objective To explore the clinical efficacy of sequential therapy with 30% supramolecular salicylic acid, CO2 fractional laser and another session of 30% supramolecular salicylic acid for patients with facial acne complicated by depressed scars. Methods A total of 66 patients with facial acne complicated by depressed scars admitted to the Department of Dermatology of Dali Bai Autonomous Prefecture People’s Hospital from December 2023 to January 2026 were selected. According to the random number table method, they were divided into control group 1, control group 2 and the observation group by the random number table method, with 22 patients in each group. Control group 1 was treated with 30% supramolecular salicylic acid, control group 2 was treated with 30% supramolecular salicylic acid+CO2 fractional laser, and the observation group was treated with 30% supramolecular salicylic acid+CO2 fractional laser+30% supramolecular salicylic acid. The treatment effect, acne severity, acne scar indicators and adverse reactions were compared among the three groups. The scab shedding time and off-work recovery time after laser treatment were compared between control group 2 and the observation group. Results The total effective rate of the observation group was 95.50%, which was higher than 54.50% of control group 1 and 72.70% of control group 2 (P <0.05). The scores of GAGS and ECCA in the three groups after treatment were lower than those before treatment, and those in the observation group were lower than those in control group 1 and control group 2 (P <0.05). There were no significant differences in the scores of GAGS and ECCA between control group 1 and control group 2 after treatment (P >0.05). The scab shedding time and off-work recovery time in the observation group were shorter than those in control group 2 (P <0.05). There was no significant difference in the incidence of adverse reactions among the three groups (P >0.05). Conclusion The combined application of 30% supramolecular salicylic acid+CO2 fractional laser+30% supramolecular salicylic acid in the treatment of facial acne complicated by depressed scars can improve clinical efficacy, alleviate acne severity, shorten scab shedding time and recovery downtime, without increasing the risk of adverse events. This regimen shows favorable safety and patient tolerance.