To explore the application effect of autologous fat granule transplantation and filling combined with double eyelid plasty in patients with upper eyelid depression. Methods A total of 70 patients who underwent upper eyelid depression correction in our hospital from December 2021 to December 2022 were selected as the research objects. According to the random number table method, they were divided into reference group and observation group, with 35 patients in each group. The reference group was given autologous fat granule transplantation and filling, and the observation group was given autologous fat granule transplantation and filling combined with double eyelid plasty. The upper eyelid depression, postoperative complications and treatment satisfaction were compared between the two groups. Results The proportion of grade 1 depression in the observation group was higher than that in the reference group, and the proportion of grade 2 and grade 3 depression was lower than that in the reference group (P <0.05). The incidence of postoperative complications in the observation group was 2.86%, which was lower than 17.14% in the reference group (P <0.05). The treatment satisfaction of the observation group was 100.00%, which was higher than 82.86% of the reference group (P <0.05). Conclusion Autologous fat granule transplantation combined with double eyelid plasty is effective in correcting upper eyelid depression, which can effectively improve the upper eyelid depression of patients, reduce the incidence of postoperative complications, and have higher patient satisfaction.