Background:: In the recent decade, there has been increasing interest in preventing ovarian toxicity after chemotherapy exposure. It has been documented that ginger (Zingiber officinale) might normalize the hormonal balance and control the menstrual cycle. Objective:: This study has analyzed whether ginger extract protects against cyclophosphamide (CP)-induced ovarian failure in rats. Methods:: Rats were distributed into four groups consisting of vehicle, CP, ginger, and CP + ginger. At the end of the treatment, all rats were killed under anesthesia to obtain ovarian tissues and blood samples for histological, molecular, and biochemical experiments. Results:: Our results indicated that ginger improves CP-caused histological changes in ovarian tissues and significantly restores serum hormonal abnormalities. Ginger also showed unique antioxidant, anti-inflammatory, and antiapoptotic properties in the ovarian tissues of CP-induced rats. Further, our findings indicated that ginger might activate the Nrf2 and SIRT and inhibit the PI3K/AKT pathway in the ovaries of CP-treated rats. In conclusion, ginger was found to protect against CP-caused ovarian toxicity in rats. Conclusion:: The protective impacts of ginger may mediate, at least partly, by alleviating the oxidant state, inhibiting pro-inflammatory conditions, and exhibiting antiapoptotic activities.