Objective To explore the efficacy and safety of low molecular weight heparin sodium gel in the repair of post-acne depressed scars treated with ultra-pulsed CO2 fractional laser. Methods A total of 38 patients with post-acne depressed scars treated with ultra-pulsed CO2 fractional laser admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from June to November 2022 were selected as the research subjects. According to the random number table method, they were divided into the control group and the experimental group, with 19 patients in each group. The control group was given medical collagen dressing, and the experimental group was given low molecular weight heparin sodium gel. The clinical efficacy, Goodman&Baron Acne Scar Grading System score and adverse reactions were compared between the two groups. Results The marked efficacy rate in the experimental group was 31.58%, which was higher than 5.26% in the control group (P <0.05). The improvement difference value of the Goodman&Baron scar scale in the experimental group was higher than that in the control group (P <0.05). The incidence of adverse reactions in the experimental group was lower than that in the control group, but the difference was not statistically significant (P >0.05). Conclusion Low molecular weight heparin sodium gel is safe and effective in the repair of post-acne depressed scars treated with ultra-pulsed CO2 fractional laser, which can effectively improve the severity of scar, and does not increase the risk of adverse reactions. It is worthy of clinical application.