Abstract: The nano-sized iron oxide (Fe 2 O 3 -NPs) is one of the most used engineered nanomaterials worldwide. This study investigated the efficacy of natural polyphenol resveratrol (RSV) (20 mg/kg b.wt, orally once daily) to alleviate the impaired sperm quality and testicular injury resulting from Fe 2 O -NPs exposure (3.5 or 7 mg/kg b.wt, intraperitoneally once a week) for eight weeks. Spermiograms, sexual hormonal levels, oxidative stress indicators, and lipid peroxidation biomarker were assessed. Moreover, the steroidogenesis-related genes mRNA expressions were evaluated. The results showed that RSV substantially rescued Fe 3 2 O -NPs-mediated sperm defects. Additionally, the Fe 2 O 3 3 -NPs-induced depressing effects on sperm motility and viability were markedly counteracted by RSV. Moreover, RSV significantly restored Fe 2 O -NPs-induced depletion of testosterone, follicle-stimulated hormone, luteinizing hormone, and testicular antioxidant enzymes but reduced malondialdehyde content. Furthermore, the Fe 2 O 3 3 -NPs-induced downregulation of steroidogenesis-related genes (3 -HSD, 17 -HSD, and Nr5A1) was significantly counteracted in the testicular tissue of RSV-treated rats. These findings concluded that RSV could limit the Fe -NPsinduced reduced sperm quality and testicular injury most likely via their antioxidant activity and steroidogenesis-related gene expression modulation. 2 O 3