Nanomaterials, due to their unique physicochemical properties, are increasingly used in various commercial and biomedical applications. However, their potential toxicity to human health remains a significant concern. This review discusses the biophysicochemical properties of nanomaterials and the available toxicology data and methodologies for evaluating nanoparticle (NP) toxicity. The review highlights the mechanisms of NP toxicity, primarily through the production of reactive oxygen species (ROS), which can cause oxidative stress and damage to cells and tissues. The review also addresses the challenges in assessing NP toxicity, including the differences between in vitro and in vivo assays, and the importance of in silico methods for predicting toxicity. The review emphasizes the need for comprehensive studies on NP toxicity to ensure the safe design and application of nanomaterials. Key factors influencing NP toxicity include size, shape, surface area, and surface chemistry. The review discusses the effects of these factors on NP toxicity, including their impact on cellular uptake, distribution, metabolism, and elimination. The review also highlights the importance of understanding the physicochemical properties of NPs to predict their toxicological effects and to develop safer nanomaterials for biomedical applications.Nanomaterials, due to their unique physicochemical properties, are increasingly used in various commercial and biomedical applications. However, their potential toxicity to human health remains a significant concern. This review discusses the biophysicochemical properties of nanomaterials and the available toxicology data and methodologies for evaluating nanoparticle (NP) toxicity. The review highlights the mechanisms of NP toxicity, primarily through the production of reactive oxygen species (ROS), which can cause oxidative stress and damage to cells and tissues. The review also addresses the challenges in assessing NP toxicity, including the differences between in vitro and in vivo assays, and the importance of in silico methods for predicting toxicity. The review emphasizes the need for comprehensive studies on NP toxicity to ensure the safe design and application of nanomaterials. Key factors influencing NP toxicity include size, shape, surface area, and surface chemistry. The review discusses the effects of these factors on NP toxicity, including their impact on cellular uptake, distribution, metabolism, and elimination. The review also highlights the importance of understanding the physicochemical properties of NPs to predict their toxicological effects and to develop safer nanomaterials for biomedical applications.