Acrylamide (AA) is a carcinogenic compound that causes severe reproductive impairments and represents a high environmental risk factor. Thymoquinone (TQ) has a unique antioxidant activity and has been widely used as a protective agent against various types of toxicity. To evaluate the protective effects of TQ against AA-induced reproductive toxicity in female rats. In this experimental study, 40 female albino rats (120-150 gr, 8-10 wk) were sorted into 4 groups, (n = 10/each), vehicle group (received a daily oral administration of 0.5 ml saline [9%]); AA group (received a daily oral administration with freshly prepared AA, 20 mg/kg body weight) for 21 days which is less than the lethal dose LD of AA in rats (20 mg/kg body weight); AA+TQ group (received a daily oral administration of TQ, 10 mg/kg body weight) after AA intoxication for 21 days, and TQ group (received a daily oral administration of TQ only, 10 mg/kg body weight) for 21 consecutive days. Reproductive hormones, carcinogenic biomarkers, and oxidative stress markers were measured. The histological assessment showed the protective effect of TQ against AA-induced ovarian injury. Network pharmacology analysis and molecular docking approach were carried out to determine the binding affinity of TQ with cyclooxygenase 2. TQ administration significantly enhanced the functional capacity of the ovary at hormones, oxidative biomarkers, and tumor markers at a significant level of p 0.001. Besides, TQ protects the ovary of AA-treated rats from the severe degeneration effect. TQ showed a promising protective effect against AA-induced reproductive toxicity in female rats.