Objective To analyze the effect of carbon dioxide (CO2) fractional laser combined with growth factor on skin physiological functions and skin aesthetics in patients with acne scar. Methods A total of 120 patients with acne scar admitted to the Department of Dermatology, Dazhou Integrated TCM&Western Medicine Hospital from October 2023 to February 2025 were selected, and they were divided into the control group and the observation group by the random number table method, with 60 patients in each group. The control group was treated with CO2 fractional laser, and the observation group was treated with CO2fractional laser combined with growth factor. The clinical efffcacy, symptom relief time, skin physiological parameters and skin aesthetics were compared between the two groups. Results The crust formation time and erythema duration of the observation group after treatment were shorter than those of the control group (P<0.05). The total effective rate of the observation group (93.33%) was higher than that of the control group (78.33%) (P<0.05). After treatment, the transepidermal water loss and stratum corneum protein content in the observation group were lower than those in the control group, and the stratum corneum hydration was higher than that in the control group (P<0.05). The ECCA score and skin melanin index of the observation group after treatment were lower than those of the control group (P<0.05). Conclusion In the clinical treatment of acne scar, CO2 fractional laser combined with growth factor therapy has a deffnite curative effect. This scheme can not only shorten the symptom relief time, effectively improve various skin physiological parameters, but also comprehensively enhance skin aesthetics.