Background: 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. Objective: To evaluate the protective effects of TQ against AA-induced reproductive toxicity in female rats. Materials and Methods: 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 LD50 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. Results: 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. Conclusion: TQ showed a promising protective effect against AA-induced reproductive toxicity in female rats. Key words: Acrylamide, Thymoquinone, Rats, Oxidative stress, Cyclooxygenase 2, Inflammation.