BACKGROUND Polycystic ovary syndrome (PCOS) is a common type of endocrinopathy in women which is accompanied by androgens elevation, insulin resistance, and metabolic dysfunction. Eugenol is a phenolic component of clove oil that has an antioxidant, anti-inflammatory, and anti-diabetic activity. The present study aimed to evaluate the therapeutic effects of eugenol on the PCOS models of rats. METHODS In this experimental study, thirty adults female Wistar rats weighing between 180 and 200 g were used. Estradiol valerate-induced PCOS rats (4 mg/rat) were treated with eugenol (12 and 24 mg/kg) for 28 days. The effects of eugenol were studied on levels of glucose, lipid profile, liver enzymes, reproductive hormones, oxidative stress, and the expression of cyclooxygenase-2 (Cox-2) and peroxisome proliferator-activated receptor alpha (Ppar-α) genes, using biochemical analysis of blood and histopathological evaluation of ovaries.<br />Results: Estradiol valerate-induced PCOS resulted in the formation of cystic follicles in the ovaries, hyperinsulinemia, hyperglycemia, hyperlipidemia, hyperandrogenism, and anovulation. It altered the Cox-2 and Ppar-α gene expression and increased oxidative stress and activities of liver enzymes. Eugenol treatment improved the PCOS-associated endocrine and metabolic disorder and histopathological alterations, mostly through antioxidant, anti-diabetic, anti hyperlipidemic, and anti-androgenic properties. It showed beneficial effects on serum glucose, serum insulin, fat profile, reproductive hormones, liver activity, oxidative stress, expression of Cox-2 and Ppar-α genes, as well as restoration of normal ovulation in the PCOS animals.<br />Conclusion: Eugenol could represent a promising natural product to prevent PCOS or reduce its symptoms.