To investigate the effect of dienogest and mirena for treating patients with adenomyosis (AM) and their influence on the levels of serum carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), mullerianin hibiting substance (MIS), and prostaglandin F2a (PGF2a) of the patients. Methods: A total of 129 patients with AM who had admitted to hospital were selected as the research objects from January 2020 to January 2022. According to random number table method, these patients were divided into two groups. 65 patients in the observation group were treated with dinorgestrol and 64 patients in the control group were treated with mirena. The clinical efficacy, the levels of serum CA125, CA199, MIS, and PGF2a, the hemorheology value, the endometrial thickness, the uterine volume change, and the adverse reactions rate of the patients in the two groups after treatment were observed. Results: After treatment, the total effective rate (96.9%) of the patients in the observation group was significantly higher than that (87.5%) of the patients in the control group. The levels of serum CA125, CA199, and PGF2a of the patients in the observation group were significantly lower than those of the patients in the control group. The MIS level of the patients in the observation group was significantly higher than that of the patients in the control group. The values of peak systolic velocity and the enddiastolic velocity of the patients in the observation group were significantly lower than those of the patients in the control group. The uterine volume (90.34±3.47 cm3) and the endometrial thickness (8.56±1.22 mm) of the patients in the observation group were significantly lower than those (101.33±3.87 cm3 and 9.04±1.22 mm) of the patients in the control group (all P＜0.05). There was no significant difference in the total adverse reactions rate (56.9% vs. 56.3%) of the patients between the two groups (P>0.05). Conclusion: Both dinorgestrel and mirena for treating the patients with AM can improve their clinical symptoms, but dinorgestrel has the better effect.