Background: Titanium dioxide nanoparticles (TDN) one of the most common nanomaterial used in a wide range of applications. Moringa oleifera leaves extract (MOLE) has hepato- and nephron-protective effects amongst other medicinal and nutritional benefits. Vitamin E (Vit. E) is an important lipid soluble vitamin. Aim: The present work aimed to study hepato-renal toxicity of TDN in adult male albino rats through biochemical and histopathological study and protective effects of either MOLE or Vit. E or both. Materials and Methods: 49 adult male albino rats were divided randomly into 7 groups (7 rats each). Group 1: served as control, Group 2: Rats received (MOLE) once daily by oral gavage Group 3: Rats received (Vit. E) once daily by oral gavage Group 4: Rats received TDN subcutaneous on alternate days Group 5: Rats coadministrated TDN and MOLE Group 6: Rats co-administrated TDN and (Vit. E), Group 7: Rats coadministrated TDN, (MOLE) and vitamin E. All groups received the treatment for four weeks, then blood samples were collected for assessment of liver function markers and kidney function markers. Also, Liver and kidney were excised for histopathological examination. Results and Conclusion: TDN treated animals recorded a significant increase in ALT, AST. ALP, total bilirubin, urea and creatinine and a significant decrease in total protein. Significant improvement occurred on co-administration of either (MOLE) or (Vit.E) or both. Histopathological lesion in both liver and kidney which were observed in TDN treated animals improved on co-administration of either (MOLE) or (Vit. E) or both.