Exposure to chemotherapeutic agents like cyclophosphamide (a drug for cancer treatment), leads to infertility due to its toxic effect on the ovaries. Combo, “a commonly used plant concoction in traditional medicine for the treatment of infertility” is composed of Clove (dried flower), garlic (bulb), ginger (rhizome), and turmeric (rhizome). The aim of this study was to evaluate the possible prophylactic effects of Combo therapy in cyclophosphamide-induced ovarian toxicity in female Wistar rats. Female Wistar rats were divided into 6 groups (A-F) of 6 animals each. Group A (normal control) received distilled water only. Group B (negative control) received 200mg/kg of cyclophosphamide only, while group C (positive control) received only 29mg/kg of Combo. On the other hand, groups D, E and F were pretreated with Combo doses of (15, 29, and 290 mg/kg) and were later treated with 200mg/kg of cyclophosphamide after 7 days. All administrations were done orally. The reproductive hormones assayed were oestrogen and progesterone, while the oxidative stress biomarkers evaluated include glutathione, malondialdehyde, and nitric oxide. Their levels were used as diagnostic markers for assessing the reproductive functions of the ovaries. Combo pre-treatment significantly (p<0.05) decreased the levels of malondialdehyde and nitric oxide, and significantly (p<0.05) increased glutathione, oestrogen and progesterone levels when compared with cyclophosphamide group. Histopathological investigation showed that Combo mitigated degenerative cells in follicles, stromal oedema, and atresia of the follicles when compared with cyclophosphamide group. In conclusion, Combo has fertility potentials and can protect against ovarian degeneration in cyclophosphamide-induced toxicity.