Objective To explore the effect of CO2 fractional laser combined with alpha hydroxy acid therapy on the skin barrier function of patients with depressed scar after acne. Methods A total of 40 patients with depressed scar after acne admitted to our hospital from October 2021 to March 2024 were selected as the research subjects, and they were randomly divided into control group and observation group, with 20 patients in each group. The control group was treated with CO2 fractional laser, and the observation group was treated with CO2 fractional laser combined with alpha hydroxy acid. The skin barrier function, subjective and objective cosmesis scores and scar symptom scores were compared between the two groups. Results After treatment, the transepidermal water loss and skin oil secretion in the two groups were lower than those before treatment, and the skin water content was higher than that before treatment. Moreover, the transepidermal water loss and skin oil secretion in the observation group were lower than those in the control group, and the skin water content was higher than that in the control group (P <0.05). After treatment, the subjective and objective cosmesis scores in the two groups were higher than those before treatment, and those in the observation group were higher than those in the control group (P <0.05). After treatment, the all dimension of VSS scores in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P <0.05). Conclusion For patients with depressed scar after acne, the application of CO2 fractional laser combined with alpha hydroxy acid therapy can effectively promote the recovery of skin barrier function, improve the subjective and objective cosmesis, and is beneficial for alleviating scar symptoms.