The present study investigated the potential role of Arctium lappa L. extract against the hepato-cardio toxicity and hyperlipidemia induced by ZnO-NPs in male rats. The groups of this study were Control, ZnO-NPs (50 mg/kg b.w.), ZnO-NPs+Arctium lappa L. (300 mg/kg b.w.) and Arctium lappa L. group. The oral administration of ZnO-NPs caused significant decrease in RBC, Hb, Hct and platelets while, WBC was increased. Liver enzymes and total bilirubin were significantly increased after ZnO-NPs supplementation. On the other hand, protein, albumin and globulin were significantly decreased in ZnO-NPs group. Lipid profile determination revealed hyperlipidemia state in the ZnO-NPs group. The ZnO-NPs group exhibited an oxidative stress as documented by an increase in TBARS and a decrease in GSH and total thiol. CK-MB, PON1, Fe+3 were significantly decreased while; LDH, TNF-α, p53, IL-6, Zn+2 and Ca+2 were increased in ZnO-NPs treated group. In addition, ZnO-NPs caused histopathological changes in liver and heart tissues. In contrast, Arctium lappa L. administration improved the most measured parameters by its antioxidant and anti-inflammatory effects against the ZnO-NPs toxicities.