To explore the efficacy of dydrogesterone in the treatment of ovarian endometriosis (EMs) after laparoscopic surgery, and to study its influence on the expression of serum human epididymis secretory protein 4 (HE4) and anti-mullerian hormone (AMH). Methods: 90 patients with ovarian EMs who wanted laparoscopic surgery were gathered and randomly separated into two groups (45 cases in each group) from January 1, 2019 to June 30, 2021. The patients in the study group were treated with gestrinone combined with dydrogesterone, and the patients in the control group were treated with gestrinone. The change of the serum HE4 and AMH levels, the pain situation, such as pain visual analog scoring (VAS), the symptom improvement situation, the clinical efficacy, and the adverse reactions of the patients were compared between the two groups. Results: After treatment, the serum HE4 and AMH levels, the degree of pelvic pain, the pain rate during intercourse, and the VAS scores of the patients in the two groups had decreased significantly, and the ranges of which of the patients in the study group were significantly more than those of the patients in the control group (P<0.05). The symptom score of the patients in the study group in 3 months after surgery was significantly lower than that of the patients in the control group (P<0.05), and there was no significant difference in the symptom score of the patients in 6 months after surgery between the two groups (P>0.05). The total remission rate of the patients in the study group (93.3%) was significantly higher than that (73.3%) of the patients in the control group (P<0.05), and there were no significant differences in the incidences of acne, transaminase elevation, weight gain, vaginal dryness, and other adverse reactions of the patients between the two groups (P>0.05). Conclusion: Dydrogesterone in adjuvant therapy of ovarian endometriosis of the patients after laparoscopic surgery can effectively reduce their serum HE4 and AMH levels, relieve their pain, improve their clinical symptoms, which is safe and effective.