Objective To analyze the effect of collagen combined with hyaluronic acid injection on the improvement of tear trough and periorbital skin in patients undergoing periorbital rejuvenation. Methods A total of 100 patients who underwent periorbital rejuvenation treatment in the Department of Injection Microsurgery, Changsha Furong FRESKIN Medical Beauty Clinic from January 2023 to January 2024 were selected as the research subjects. According to the random number table method, they were divided into the control group (n =50) and the observation group (n =50). The control group was treated with hyaluronic acid injection, and the observation group was treated with collagen combined with hyaluronic acid injection. The tear trough improvement, periorbital skin improvement, quality of life and complications were compared between the two groups. Results After treatment, the scores of tear trough, malar fat pad ptosis, pigmentation and skin fold wrinkle in the observation group were lower than those in the control group (P <0.05). The improvement of skin laxity, double eyelid width and fishtail lines in the observation group were higher than those in the control group (P <0.05). After treatment, the scores of all aspects of the quality of life in the observation group were higher than those in the control group (P <0.05). There was no significant difference in the incidence of complications between the two groups (P >0.05). Conclusion The application of collagen combined with hyaluronic acid injection in periorbital rejuvenation treatment can effectively improve the tear trough and periorbital skin, help to improve the quality of life, and reduce the risk of complications, which is worthy of clinical application.