Objective: To investigate the clinical efficacy of mifepristone in the treatment of uterine adenomyosis complicated with severe anemia and its effect on iron metabolism. Methods: 72 patients with adenomyosis combined with severe anemia admitted to our hospital from January 2022 to October 2024 were selected as the study objects. The patients were divided into control group and study group by random number table method, 36 cases in each group. The control group was treated with traditional hormone therapy (pregnrienone) combined with iron, folic acid and non-steroidal anti-inflammatory drugs. The study group was treated with mifepristone combined with iron, folic acid and non-steroidal anti-inflammatory drugs. Clinical symptoms (VAS score, PBAC score), uterine status (uterine volume, endometrial thickness), degree of anemia (hemoglobin level), iron metabolism index [(serum iron (Fe) and total iron binding capacity (TIBC)], quality of life (SF-36 score), and adverse events of the two groups were analyzed and compared. Results: After treatment, VAS scores and PBAC scores of both groups were significantly lower than before treatment, and VAS scores and PBAC scores of the study group were significantly lower than those of the control group after treatment (P < 0.05). After treatment, the uterine volume and endometrial thickness of the two groups were significantly increased than before treatment, and the hemoglobin level was significantly increased than before treatment, and the changes in the uterine volume, endometrial thickness and hemoglobin level of the study group after treatment were significantly greater than those of the control group (P < 0.05). After treatment, Fe and TIBC in both groups were significantly higher than before treatment, and Fe and TIBC in the study group were significantly higher than those in the control group after treatment (P < 0.05). After treatment, the SF-36 score of quality of life in both groups was significantly lower than that before treatment, and the SF-36 score of the study group after treatment was significantly lower than that of the control group (P < 0.05). There were no obvious adverse reactions during treatment in both groups. Conclusion: Mifepristone in the treatment of uterine adenomyosis complicated with severe anemia can alleviate clinical symptoms, reduce uterine volume, improve iron metabolism, and improve quality of life, with high safety.