Objective To explore the effect of ultrapulsed fractional CO2 laser combined with mucopolysaccharide polysulfate cream on TCM syndrome scores in patients with facial depressed acne scar. Methods A total of 60 patients with facial depressed acne scar admitted to the Department of Dermatovenereology, Xinghua City People's Hospital from January 2023 to December 2024 were selected as the research subjects. According to the random number table method, they were divided into the reference group and the treatment group, with 30 patients in each group. The reference group was treated with mucopolysaccharide polysulfate cream alone, and the treatment group was treated with ultrapulsed fractional CO2 laser combined with mucopolysaccharide polysulfate cream. The clinical efficacy, TCM syndrome scores, inflammatory factor indexes and adverse reaction rate were compared between the two groups. Results The total effective rate of the treatment group (83.33%) was higher than that of the reference group (56.67%) (P<0.05). After treatment, the scores of facial ffushing, skin rash, itching and pain in the treatment group were lower than those in the reference group (P<0.05). After treatment, the levels of tumor necrosis factor-α and interleukin-1β in the treatment group were lower than those in the reference group (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Ultrapulsed fractional CO2 laser combined with mucopolysaccharide polysulfate cream in the treatment of facial depressed acne scar can improve acne-related symptoms and inffammatory factor levels, with few adverse reactions.