Objective To study the clinical effect of photodynamic therapy combined with recombinant type Ⅲ humanized collagen scar gel in the treatment of moderate to severe acne depressed scar. Methods A total of 92 patients with moderate to severe depressed scars admitted to the dermatology department of our hospital from July 2022 to January 2023 were selected as the research objects. They were divided into conventional group and combined group by random number table method, with 46 patients in each group. The conventional group was treated with photodynamic therapy, and the combined group was treated with recombinant type Ⅲ humanized collagen scar gel on the basis of the conventional group. The clinical efficacy, acne scar score, psychological state and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the combined group was 95.65%, which was higher than 82.61% in the conventional group, and the difference was statistically significant (P<0.05). After treatment, the ECCA score of the combined group was (0.51±0.22) scores, which was lower than (1.52±0.36) scores of the conventional group, and the difference was statistically significant (P<0.05). The scores of anxiety and depression in the combined group were lower than those in the conventional group, and the differences were statistically significant (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Photodynamic therapy combined with recombinant type Ⅲ humanized collagen scar gel can improve the clinical efcacy, reduce acne scar score and improve the psychological state of patients with moderate to severe acne scars. It is safe and worthy of clinical application.