This study aims to compare the clinical efficacy of myomectomy and total hysterectomy in the treatment of perimenopausal uterine fibroids. 124 cases of uterine fibroids were randomly divided into a control group and a study group, each with 62 cases. The control group underwent a total hysterectomy. Study participants underwent a myomectomy. Both groups of patients were observed and compared for surgery-related indicators, quality of life scores, perimenopausal syndrome and inflammatory factors. The study group had a shorter operation time and less intraoperative blood loss (p < 0.05). Before operation, there was no significant difference in Quality of life Short Form 36 (SF-36) score, Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-10 between both groups (p > 0.05) at 6 months after operation, SF-36 score in both groups were higher than before operation, and IL-6, TNF-α and IL-10 in both groups were higher than before operation (p < 0.05). Perimenopausal syndrome incidence was significantly lower in the study group than in the control group (p < 0.05). Myomectomy is more suitable for treating perimenopausal uterine fibroids.