Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one of the top five most commonly used nanoparticles worldwide. Recently, various studies referred to their toxic potential on various organs using different treatment route. The present study was carried out to evaluate the potential protective role of blackberry and selenium (Se) against (TiO2NPs)-induced oxidative stress and histological changes in liver and heart tissues of rats. Rats were divided into seven groups according to the treatment into control, Titanium dioxide treated group (TiO2NPs) (500 mg/kg b.w.), Black berry (Bb) treated group (1.6 g/kg body), Selenium (Se) (0.5 mg/kg;), (TiO2NPs)plus Bb and (TiO2NPs)plus Se and the last group treated with combination of (TiO2NPs) plus Bb and Se. All the Animals were treated orally for 30 successive days. (TiO2NPs) increased alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) activities and changed the levels of lipid profile as well as creatinine and uric acid levels. It marked decreased hepatic reduced glutathione (GSH) levels, antioxidant enzymes activities and increased the levels of lipid peroxidation, C-reactive protein and interleukins. Bb and Se prevented the (TiO2NPs)-induced liver and heart injury as indicated by improving all the parameters previously illustrated. Histopathological results confirm the biochemical finding and the ameliorating effect of both Bb and Se on liver toxicities and heart failure. In conclusion, co-treatment of either Bb or Se possessed different protective mechanisms against (TiO2NPs)-induced liver toxicity and heart damage. So, the intake of (TiO2NPs) should be restricted due to its increased toxicity.