Objective To observe the effect of ultra-pulsed carbon dioxide fractional laser combined with local dermabrasion in the treatment of moderate to severe acne scar and its influence on skin barrier function. Methods A total of 62 patients with moderate to severe acne scar admitted to our hospital from January 2019 to June 2023 were selected. According to different treatment methods, they were divided into the control group and the observation group, with 31 patients in each group. The control group received ultra-pulsed carbon dioxide fractional laser treatment, and the observation group received the combination of ultra-pulsed carbon dioxide fractional laser and local dermabrasion. The clinical efficacy, skin barrier function and adverse reactions were compared between the two groups. Results The total effective rate in the observation group (96.77%) was higher than that in the control group (80.65%) (P <0.05). At 1 and 3 months after treatment, the transepidermal water loss and stratum corneum hydration in the two groups were better than those before treatment (P <0.05). At 1 month after treatment, the transepidermal water loss in the observation group was lower than that in the control group, and the stratum corneum hydration was higher than that in the control group (P <0.05). However, there was no significant difference in stratum corneum hydration and transepidermal water loss between the two groups at 3 months after treatment (P >0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion Ultra-pulsed carbon dioxide fractional laser combined with local dermabrasion has a good effect in the treatment of moderate to severe acne scar, which is conducive to the short-term self-repair of skin barrier function, with higher application safety.