The current research was planned to evaluate the ameliorative role of juglanin (Jug) against polyethylene microplastics (PEMP) prompted testicular impairments. 48 rats were allocated in 4 groups: control, PEMP exposed, Jug + PEMP co-administrated and Jug supplemented group. The activities of antioxidant enzyme, inflammatory markers level, hormonal level, the expressions of steroidogenic enzymes, pro-apoptotic and anti-apoptotic protein were assessed after the 56 days of the trial. PEMP intoxication significantly disturbed Nrf-2/Keap-1 pathway and the biochemical profile of rats. However, the administration of Jug markedly increased Nrf-2 and anti-oxidant enzymes expressions, besides decreased the Keap-1 expression. Jug administration also increased Catalase (CAT), super oxide dismutase (SOD) glutathione reductase (GPx), glutathione peroxidase (GSR) and Hemeoxygenase-1 (HO-1) activities. On the other hand, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased following Jug administration. Moreover, Jug administration decreased the levels of inflammatory markers. Additionally, Jug administration increased luteinizing hormone (LH), testosterone, follicle-stimulating hormone (FSH) levels and steroidogenic enzymes expression including 17β-hydroxysteroid dehydrogenase (17β-HSD), steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) expressions. Jug administration decreased Caspase-3 and Bax expressions, while increasing Bcl-2 expression. Therefore, the current findings suggested that Jug can remarkably alleviate PEMP induced testicular damage due to its therapeutical potentials.