Background: Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women of reproductive age, which may affect various organs, including the brain and liver. Objectives: This study aimed to investigate the potential ameliorating effects of black seed (Nigella sativa) hydroethanolic extract on the liver and brain tissues in a rat model of polycystic ovary. Methods: In this experimental study, eighteen female rats were divided into three groups: control (PCO rats on day 0 after induction of PCO), vehicle (PCO rats receiving saline via gavage for 28 days), and black seed extract (BSE) (PCO rats receiving BSE via gavage for 28 days). Polycystic ovary was induced by a single intraperitoneal injection of 2 mg/kg estradiol valerate. Liver tissue was evaluated for the average number of damaged hepatocytes (segmented nucleus and cytoplasm shrinkage), number of Kupffer cells, and number of lipid droplets, while brain tissue was assessed for vacuolization, apoptosis, and cell shrinkage. Results: In the BSE group, liver weight significantly decreased, while brain weight increased compared to the vehicle and control groups. Moreover, there was a significant decrease in the number of damaged hepatocytes and Kupffer cells in the BSE group compared to the vehicle group in the liver tissue. In the brain tissue, there was a significant reduction in the number of vacuolations in the BSE group compared to the vehicle group. Conclusions: Black seed extract demonstrated potential ameliorating effects on the adverse impacts of PCO in the liver (reducing damaged hepatocytes and Kupffer cells) and brain (reducing vacuolations). Further histologic and molecular analyses are needed to investigate the protective effects of BSE thoroughly.