Objective To explore the effect of poly-L-lactic acid (PLLA) microsphere injection on skin thickness and aesthetic score in female patients with temporal and tear trough depression. Methods A total of 60 patients with temporal and tear trough depression who received facial filling treatment in the Department of Aesthetic Surgery, White Collar Angel Women and Children’s Hospital of Hefei from January to October 2024 were selected, and they were divided into the control group and the study group by the random number table method, with 30 patients in each group. The control group was given sodium hyaluronate injection, and the study group was given PLLA microsphere injection. The skin thickness, aesthetic score, adverse reaction rate and patient satisfaction were compared between the two groups. Results The skin thickness in the study group at 1, 3, and 6 months after operation was better than that in the control group (P <0.05). The aesthetic score in the study group at 1 and 3 months after operation was better than that in the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). The satisfaction rate in the study group (96.67%) was higher than that in the control group (86.67%)(P <0.05). Conclusion The application of PLLA microsphere injection in filling temporal and tear trough depression can effectively improve tissue remodeling effect, optimize facial contour, with prominent aesthetic effect and high patient satisfaction.