Objective To investigate the effect of fractional laser combined with microneedle therapy on the improvement of skin physiological indicators in patients with depressed acne scars. Methods A total of 80 patients with depressed acne scars treated in our hospital from December 2024 to December 2025 were selected. According to the random number table method, they were divided into the control group and the observation group, with 40 patients in each group. The control group received microneedle therapy, and the observation group received fractional laser combined with microneedle therapy. The clinical efficacy, improvement of skin physiological indicators and adverse reaction rate were compared between the two groups. Results The total effective rate of the observation group was 95.00%, which was higher than 77.50% of the control group (P <0.05). At 1 month after treatment, the VISIA pore score, red area score and TEWL level of the two groups were lower than those before treatment, and those of the observation group were lower than those of the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion The application of fractional laser combined with microneedle therapy in the treatment of depressed acne scars can effectively improve clinical efficacy, improve the skin texture and barrier function, and does not increase the risk of adverse reactions, which is worthy of clinical application.