Polycystic ovary syndrome (PCOS) is a proinflammatory/oxidative state resulting in metabolic dysregulation and ovarian dysfunction. Isoflavones in soybean seed possess anti-inflammatory/antioxidant properties. So, in this study, the effects of soybean isoflavone-aglycones on tissue inflammation, oxidative status, and ovarian histology in an animal model of PCOS were considered to achieve a novel therapeutic agent. Thirty-two female Wistar rats were divided into four groups (n = 8): a control group receiving the vehicle (CON-); a group with PCOS receiving no treatment (PCOS); and two groups of PCOS rats treated with soybean isoflavone-aglycone fraction (SISAF) at 50 and 100 mg/kg (SISAF50 and SISAF100). PCOS was induced by injecting a single dose of estradiol valerate (4 mg/kg, IM) dissolved in 0.2 ml of sesame oil following 60 days for the full development of polycystic ovaries. The SISAF treatments were administered orally once a day for 21 days. Then, the ovaries were harvested for the assessment of oxidative/antioxidative parameters, interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels concomitant with histological studies. Treatment with SISAF reduced the number of cystic follicles and thickness of the theca layer, as well as increasing the number of corpora lutea and granulosa cells in PCOS rats. Also, SISAF treatment significantly decreased ovarian tissue IL-6 and TNF-α levels, and improved total oxidative/antioxidative status compared to the PCOS group. Isoflavones may provide therapeutic effects in PCOS owing to the antioxidant and anti-inflammatory properties.