One of the major contaminants in aquatic ecosystems is bisphenol A (BPA), a synthetic industrial chemical widely used in the production of epoxy resins and plastics. BPA has negative effects on fish health. Proanthocyanidin, a natural immune stimulant extracted from grape seeds (GR), possesses various biological and antioxidant properties. This study aimed to mitigate the harmful effects of BPA by supplementing the fish diet with GR. Healthy Nile tilapia (120 fish, 14.95±0.10g) were divided into four groups: Group 1 served as the control; group 2 was fed 400mg GR per kg of feed; group 3 was exposed to 3mg of BPA per liter of water without GR supplementation, and group 4 was exposed to 3mg of BPA per liter of water and fed a GR-supplemented diet (400mg GR per kg). After 28 days, blood and tissue samples were collected to assess serum biochemical parameters, cytokines, catalase (CAT) activity, malondialdehyde (MDA) levels, and the histological features of the liver, spleen, and kidney. Co-treatment with GR improved serum protein levels as well as urea and creatinine levels that were previously altered by BPA exposure. BPA exposure elevated serum interleukin (IL)-1β and hepatic MDA levels, which were reduced by GR administration. Additionally, CAT activity decreased in the BPA group but increased in the GR+BPA group. BPA also significantly upregulated the mRNA transcripts of IL-6 and tumor necrosis factor (TNF-α), which may trigger inflammation, while GR significantly downregulated these genes in the BPA-treated group. Histological analysis showed that GR alleviated tissue damage caused by BPA. In conclusion, GR supplementation improved fish biochemical and histological parameters and mitigated the toxic effects of BPA.