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Iron oxide nanoparticles (IONPs) possess many utilizable physical and chemical properties and have an acceptable level of biocompatibility. Therefore, they are extensively used in different medical applications. Hence, the challenge is to modify the surfaces of prepared iron oxide nanoformulations with a biocompatible coat to enhance their biosafety. In this study, different formulations of IONPs with different capping agents (citrate [Cit‐IONPs], curcumin [Cur‐IONPs], and chitosan [CS‐IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit‐IONPs, Cur‐IONPs, CS‐IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4 mg/kg of body weight/day. The results were compared with a control group injected orally with saline. The iron content in the kidneys, liver, and spleen was measured by atomic absorption spectroscopy. Histopathological alterations were also examined. The biodistribution results demonstrate that iron accumulated mainly in the liver tissue, whereas the lowest liver accumulation was observed after the administration of Cit‐IONPs or CS‐IONPs, respectively. In contrast, the administration of CS‐IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO4)‐treated group showed the highest kidney iron accumulation as compared with the other groups. The histopathological examination revealed that signs of toxicity were predominant for groups treated with Cit‐IONPs or commercial FeSO4. However, Cur‐IONPs and CS‐IONPs showed mild toxicity when administered at the same doses. The results obtained in the present study will provide insights into the expected in vivo effects after administration of each nanoformulation. [ABSTRACT FROM AUTHOR]