Objective To compare the effects on the establishment of the mouse model of diminished ovarian reserve (DOR) by tripterygium wilfordii polyglycosides, cyclophosphamide and cisplatin. Methods Mice were randomly divided into blank group, tripterygium wilfordii polyglycosides (TWP) group, cyclophosphamide (CTX) group and cisplatin (DDP) group. Mice in TWP group were treated with 50 mg/kg tripterygium glycoside suspension by gavage for 14 days, mice in CTX group were treated with 20 mg/kg cyclophosphamide suspension by intraperitoneal injection for 14 days, and mice in DDP group were intraperitoneally injected with 1.5 mg/kg cisplatin solution for 14 days. The body weight, uterine index and ovarian index of mice were recorded; the estrous cycle of mice was observed by vaginal smear method; the levels of anti-Mullerian hormone (AMH), estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were detected by ELISA; HE was used to detect ovarian follicle development; The maturation rate of oocytes and fertility of mice were analyzed. Results The body weight and ovarian index of the three groups of mice were significantly decreased (P < 0.05); the estrous cycle appeared disorder, with the level of AMH and E2 was significantly decreased (P < 0.05); the rate of developing follicles was decreased, and the rate of atretic follicles was increased (P < 0.05); the maturation rate of oocytes, the pregnancy and live birth were significantly decreased (P < 0.05). Conclusions The DOR mice models were successfully constructed by tripterygium glycosides, cyclophosphamide and cisplatin. the body weight and ovarian index were decreased, the estrous cycle and hormone appeared disorder, and the ovarian reserve function were decreased, resulted in the reduction rate of oocyte maturation, pregnancy and total number of live births; the effect of diminished ovarian reserve was more appropriate in the cyclophosphamide group.