Objective To explore the clinical effect of fat granular transplantation in patients with upper eyelid depression. Methods A total of 82 patients with upper eyelid depression admitted to our hospital from July 2021 to July 2022 were selected as the research objects. They were divided into reference group and study group by random number table method, with 41 patients in each group. The reference group was treated with double eyelid incision combined with massive fat transplantation, and the exploration group was treated with fat granular transplantation. The clinical efficacy and treatment satisfaction of the two groups were compared. Results The total effective rate of treatment in the study group was 100.00%, which was higher than 90.24% in the reference group (P<0.05). The treatment satisfaction of the study group was 97.56%, which was higher than 80.49% of the reference group (P<0.05). Conclusion The clinical effect of fat granular transplantation in patients with upper eyelid depression is good, which can effectively improve the upper eyelid depression of patients and improve the satisfaction of treatment.