To determine the protective effect of Dendrobium officinale polysaccharide (DOP) on ovarian and embryonic development of female mice with reproductive damage induced by cyclophosphamide (CP), 150 female Kunming mice were randomly separated into the following 6 groups (n=25): control; DOP(200mg/kg); CP; CP+DOP_L(100mg/kg); CP+DOP_M (200 mg/kg); and CP +DOP_H(400 mg/kg). On day 0, each group received an intraperitoneal injection of CP (75mg/kg), and the control and DOP groups received an intraperitoneal injection with sterile physiologic saline. The DOP and CP+DOP_(L/M/H) groups received intragastric doses of DOP, and the CP and control groups received intragastric dosed of physiologic saline in the same amount for 7 d. At the conclusion of intragastric dosing on d 7, ten mice were randomly sacrificed in each group. The ovarian indices were calculated. The ovarian tissues stained with hematoxylin and eosin and the pathologic changes were noted. The number of follicles at different stages were counted with the aid of a microscope. The malondialdehyde (MDA) and superoxide dismutase (SOD) content in ovarian tissues was detected using a chemical method. The remaining 15 mice in each group were mated with male mice after superovulation. Four of the mice were sacrificed 2.5 d after the appearance of a vaginal plug to assess embryonic development. Four of the mice were sacrificed on d 6.5 and the number of embryo implantation sites was measured with the aid of trypan blue staining. The remaining four mice were sacrificed on d 12.5 to calculate embryonic development at different stages and the non-viable embryo rate. CP significantly reduced the number of follicles at different stages and increased the number of atretic follicles in the ovaries of female mice. Also, CP affected embryo development and significantly increased the embryo death rate. CP treatment also significantly increased the MDA content in ovarian tissues and significantly reduced SOD activity. When CP and different doses of DOP were co-treated, the number of follicles at different stages in the ovary was increased and the number of follicles was reduced (P<0.05). Superovulation and in vivo fertilization experiments showed that DOP increased the percentage of embryos at different stages, especially the percentage of 8-cell embryos (P<0.05), and significantly reduced the percentage of broken embryos (P<0.05). DOP treatment also increased the number of embryo implantation sites (P<0.05) and reduced the rate of dead embryos (P<0.05). In addition, medium and high doses of DOP reduced the MDA content (P<0.001) and increased the SOD activity (P<0.001) in ovarian tissues. CP caused ovarian follicle loss in mice and severely affected embryonic development. DOP effectively alleviated reproductive injury in female mice caused by CP. At a DOP dose ≥200 mg/kg, the effect was more obvious. The therapeutic effects of reproductive damage was related to the antioxidant effects.