Superparamagnetic iron oxide nanoparticles (SPION) are widely used in biomedical applications such as magnetic resonance imaging, drug delivery, and hyperthermia. Despite their potential benefits, concerns about their toxicity and cellular effects remain. This review discusses the potential toxicity of SPION, focusing on their ability to induce cellular stress, DNA damage, and oxidative stress. SPION can cause cellular perturbations such as changes in the actin cytoskeleton, gene expression, iron homeostasis, and signaling pathways. The interaction between SPION and proteins is also important, as it can influence cellular uptake and toxicity. The review also highlights the importance of surface coating in determining the toxicity of SPION, as different coatings can affect their biological behavior and interactions with cells. The study of SPION toxicity is crucial for ensuring their safe use in biomedical applications. The review also discusses the mechanisms of SPION toxicity, including the generation of reactive oxygen species, iron overload, and the potential for DNA damage. The review concludes that further research is needed to fully understand the biological effects of SPION and to ensure their safe use in medical applications.Superparamagnetic iron oxide nanoparticles (SPION) are widely used in biomedical applications such as magnetic resonance imaging, drug delivery, and hyperthermia. Despite their potential benefits, concerns about their toxicity and cellular effects remain. This review discusses the potential toxicity of SPION, focusing on their ability to induce cellular stress, DNA damage, and oxidative stress. SPION can cause cellular perturbations such as changes in the actin cytoskeleton, gene expression, iron homeostasis, and signaling pathways. The interaction between SPION and proteins is also important, as it can influence cellular uptake and toxicity. The review also highlights the importance of surface coating in determining the toxicity of SPION, as different coatings can affect their biological behavior and interactions with cells. The study of SPION toxicity is crucial for ensuring their safe use in biomedical applications. The review also discusses the mechanisms of SPION toxicity, including the generation of reactive oxygen species, iron overload, and the potential for DNA damage. The review concludes that further research is needed to fully understand the biological effects of SPION and to ensure their safe use in medical applications.