Objective To investigate the clinical efficacy of the triple sequential chemotherapy (ACM) regimen in the treatment of trophoblastic tumors and its ovarian function protection value. Methods A total of 82 patients with trophoblastic tumors who visited Yongmei Coal Group General Hospital between May 2021 and November 2023 were selected as the study subjects and randomly divided into the control group and the observation group, with 41 cases in each group. The 41 cases in the control group were given 5-fluorouracil combined with Actinomycin D (Act-D) chemotherapy, and the 41 cases in the observation group were given the ACM regimen of Act-D, Cytoxan (CTX), and methotrexate (MTIX), and the two groups were compared in terms of clinical efficacy, ovarian reserve function, temporary amenorrhea rate and adverse effects. Results After 2 courses of treatment, the objective remission rate of the observation group was higher than that of the control group (P<0.05). The levels of estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in patients of the two groups were all reduced (P<0.05), and those were lower in the observation group (P <0.05). Serum anti-müllerian hormone (AMH) levels were increased in both groups (P <0.05) and those were higher in the observation group (P<0.05). There was no significant difference in the rate of temporary amenorrhea between the two groups (P>0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The ACM regimen is efficacious in treating patients with trophoblastic tumors, and its sequential pattern of drugs may attenuate ovarian reserve impairment.