Different materials are used as barriers to protect patients and medical staff in hospital radiological areas. A suitable shielding material needs to have a high atomic number (high Z) to protect against X-ray or gamma radiation, such as lead (Pb), barium (Ba), and bismuth (Bi). However, traditional shielding materials have cost, weight, and toxicity limitations. Therefore, there is a need for alternative materials for radiation shielding, one of which could be polymeric matrix nanocomposites. These materials have important properties such as elasticity, biocompatibility, low cost, and lightness, making them good candidates for attenuating different types of radiation. This study focuses on synthesizing different oxides and their use in developing polyvinyl chloride (PVC)-based polymeric nanocomposites. The structural and morphological properties of oxides and nanocomposites were studied using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The X-ray shielding property for the radiodiagnostic energy range of 50 to 129 kV was measured according to the mass attenuation coefficient (μm), half-value layer (HVL), and tenth-value layer (TVL). The flexible nanocomposites were cross-linked with ionizing radiation treatments to enhance their toughness and further analyzed for their cytotoxic properties. This analysis involved exposing the nanocomposites to 1132sk fibroblast cells and measuring their viability, providing insight into the safety of these materials for medical applications.