Recently, many biological fields including medicine, personal care products, sunscreens and food additives, also many industrial domains such as ceramics, rubber, paints and alloys, have been extensively applied by Zinc oxide nanoparticles (ZnO NPs), as it has the ability to pass through the cell membrane easily and even pass through blood-brain barrier. They are highly reactive and may cause oxidative stress, which induces serious damages in DNA and protein structures forming mutation. So, the current study was designed to assess the possible mitigating effect of Artemisia judaica (Art. j.), vitamin C (vit. C) or their co-administration against ZnO NPs–induced hepatorenal toxicity in male rats. Eighty adult male rats were divided into 8 groups: the 1^st (control group) with distilled water for 45 days; the 2^nd (twin 80 group) with twin 80 for 45 days; the 3^rd (ZnO NPs group), rats were gavaged daily with 10 mg/kg body weight (b.wt) of ZnO NPs for 15 days; the 4^th (vit. C group), rats were gavaged daily with 100 mg/kg b.wt of vit. C for 30 days; the 5^th (Art. j. group), rats were gavaged daily with 150 mg/kg b.wt of Art. j. extract for 30 days; the 6^th (ZnO NPs + vit. C group), rats were gavaged daily with 10 mg/kg b.wt of ZnO NPs for 15 days then gavaged daily with 100 mg/kg b.wt of vit. C for 30 days; the 7^th (ZnO NPs + Art. j. group), rats were gavaged daily with 10 mg/kg b.wt of ZnO NPs for 15 days then gavaged daily with 150 mg/kg b.wt of Art. j. for 30 days; the 8^th (ZnO NPs + vit. C and Art. j. group), rats were gavaged daily with 10 mg/kg b.wt of ZnO NPs for 15 days then gavaged daily with Art. j. and vit. C co-administration for 30 days. ZnO NPs group showed a high significant increase in serum alanine aminotransferase (ALT), aspartate amino transferase (AST), alkaline phosphatase enzyme (ALP) and gamma glutamyltransferase(GGT) activities, serum total and direct bilirubin, creatinine, urea and uric acid levels, and blood urea nitrogen (BUN) and malondialdhyde (MDA) levels. While, it showed a high significant decrease in serum albumin, protein and reduced glutathione (GSH) levels, serum superoxide dismutase (SOD), glutathione peroxidase (GP_X) and catalase (CAT) activities, as well as blood hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and packed cell volume (PCV) as compared with control group. ZnO NPs groups that were treated by vit. C or Art. j. showed partial ameliorative effect against ZnO NPs-induced hepatorenal toxicity with convergent degree, but the efficacy of Art.j. was better than vit. C. ZnO NPs group that was treated by vit. C and Art. j. co-administration showed marked significant curative effects against ZnO NPs- induced hepatorenal toxicity.