OBJECTIVE: This study combines toxicology, analytical chemistry, and nanotechnology to develop cerium oxide nanoparticles, both uncoated and coated with Polyethylene Glycol and Polyvinylpyrrolidone polymers. The objective is to assess their toxicity reduction using cell-based assays. METHODS: Nanoparticles were synthesized using the co-precipitation technique. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were employed to characterize their properties. The MTT assay evaluated cell viability, whereas reactive oxygen species and LPO assays were used to quantify oxidative stress. FINDINGS: The chemical analysis of nanoparticles of the study revealed that cerium oxide nanoparticles exhibited better and more regular morphological characteristics compared to nanoparticles coated with PEG and PVP polymers in terms of size. In addition, cerium oxide nanoparticles combined with PVP polymer did not retain the morphology at the nano level. Toxicological studies demonstrated a reduction in the toxicity of cerium oxide nanoparticles when coated with PEG and PVP polymers. DISCUSSION AND CONCLUSION: The study found that PEG coating significantly reduces the cytotoxicity of cerium oxide nanoparticles more effectively than PVP coating by mitigating oxidative stress. This approach presents a promising strategy for developing safer cerium oxide-based products for pharmaceutical and medical applications.