Objective To compare the effects of Tripterygium wilfordii polyglycosides, cyclophosphamide, and cisplatin on the establishment of a mouse model of diminished ovarian reserve (DOR). Methods Mice were randomly divided into the following treatment groups: control (Ctrl), Tripterygium wilfordii polyglycosides (TWP), cyclophosphamide (CTX), and cisplatin (DDP). Mice in the TWP group received a 50 mg/kg suspension of Tripterygium wilfordii polyglycosides by gavage for 14 days, mice in the CTX group received a 20 mg/kg cyclophosphamide suspension by intraperitoneal injection for 14 days, and mice in the DDP group received a 1.5 mg/ kg cisplatin solution by intraperitoneal injection for 14 days. The body weight, uterine index, and ovarian index were recorded, the estrous cycle was monitored using the vaginal smear method , and the levels of anti-Mullerian hormone (AMH), estradiol (E2 ), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were detected using ELISA. Hematoxylin and eosin staining was used to detect ovarian follicle development. The rates of oocyte maturation and fertility were analyzed. Results The three treatment groups of mice all showed the following: significantly decreased body weight and ovarian index (P<0.05); apparent disorder of the estrous cycle; significantly decreased levels of AMH and E2 (P<0.05); decreased and increased rates of developing follicles and atretic follicles, respectively (P<0.05); and significantly decreased rates of oocyte maturation, pregnancy, and live birth (P<0.05). Conclusions DOR mouse models were successfully constructed using Tripterygium wilfordii polyglycosides, cyclophosphamide, or cisplatin, as evidenced by decreased body weight and ovarian index, disordered estrous cycle and hormones, and DOR function, resulting in reduced rates of oocyte maturation, pregnancy, and total number of live births. These DOR effects were most appropriate in the cyclophosphamide group.