Objective: To investigate ameliorative effects of Vitex agnus-castus (VAC) and VAC containing pharmaceutical supplement (VPS) against polycystic ovary syndrome (PCOS). Methods: PCOS in the rats was induced by daily administration of letrozole at 1 mg/kg body weight concentration for 21 d. PCOS rats were then treated daily either with metformin, VAC plant extract or VPS at 70, 8 or 8 mg/kg body weight concentration for 15 d. Rats that received none of these treatments were considered as control. Blood and ovaries were collected from all the rats. Serum glucose, cholesterol, triglyceride and high density lipoprotein-cholesterol were measured spectrophotometrically. Serum insulin, estrogen, progesterone, testosterone, luteinizing hormone, follicle-stimulation hormone, catalase, superoxide dismutase, malondialdehide and reduced glutathione were measured using enzyme-linked immunosorbent assay. Results: Rats treated with letrozole demonstrated a significant increase in serum testosterone, estrogen, cholesterol, luteinizing hormone, triglycerides, glucose, insulin, and malondialdehide levels, and a significant decline in progesterone, follicle-stimulating hormone, high density lipoprotein-cholesterol, catalase and reduced glutathione levels compared to control. Contrarily, no significant change in superoxide dismutase was noted in response to letrozole treatment. Rats treated with metformin, VAC or VPS showed a remarkable reversal in the levels of parameters affected by letrozole treatment. Conclusions: Data indicate that VAC and VPS exert potential ameliorative effects against PCOS through the modulation of hormonal and lipid profile as well as oxidative stress. Moreover, the favorable effects of these compounds are comparable to that of metformin.