<p>Chromium oxide nanoparticles (Cr₂O₃ NPs) is a promising material that is widely used in various industries as a pigment or a catalyst. However, there is a certain limitation on the use of nanoscale form owing to its toxic effects on body health. Therefore, the present study aimed to investigate the physicochemical properties of Cr₂O₃ NPs obtained via coprecipitation at different calcination temperatures and to assess the toxicological effects of precipitated NPs on the different parenchymatous organs. Our findings demonstrated that the higher calcination temperature promoted the crystal properties of the Cr₂O₃ NPs by increasing the particle size, decreasing the band gap, enhancing the morphology of the crystal, and improving the colloidal stability. However, reducing both oxygen vacancies and crystal defects by eliminating voids and microstructure defects. The animal study showed a remarkable increase in the toxicity features within the parenchymatous organs of commercial Cr₂O₃ NPs, with prominence, whereas the calcined Cr₂O₃ groups showed a noticeable decrease in the toxicity within these organs. Animals administered with commercial Cr₂O₃ showed systemic inflammatory lesions and disruption of the antioxidant status associated with increased MDA level, decreased SOD and CAT levels, and downregulation of Nrf2 and HO-1 mRNA levels in within the hepatic, renal,and cardiac tissues, whereas the other calcined groups, especially animals treated with 800°C-calcined Cr₂O₃, showed a marked decrease in the inflammatory alterations and restored the antioxidant enzymes and genes to the normal limits. Therefore, an increase in the calcination temperature markedly reduced the toxicological effect of Cr₂O₃ NPs, which, in turn, effectively enhanced their biological benefits.</p>