In this research, for the first time, lead oxide nanoparticles (PbO-NPs) were synthesized using Trigonella feonumgraecum plant seeds as a stabilizer and Pb (NO3)2 salt as lead precursor. The results of the XRD pattern displayed the synthesized NPs have an orthorhombic crystalline structure. According to FESEM images, the NPs had a mean size of about 18.62 nm with a spherical morphology. Also, the cytotoxicity of NPs was evaluated on the Hep G2 cancer cell line, and the IC50 value was reported as 267.07 μg/mL. Next, the photocatalytic performance of the synthesized PbO-NPs was investigated for removing methylene orange (MO) pigment under UVA light, which led to the destruction of about 94% after 120 min. Finally, to investigate the protective property of PbO-NPs against X-ray, a polymer nanocomposite of epoxy resin/PbO-NPs was prepared with different weight percentages. In the same way, other samples were also prepared, and then their ability to attenuate X-ray was studied with an X-ray tube with a voltage of 52 kV for the palm and 80 kV for the thigh of an average person, respectively. The measurement results show that with the increasing weight percentage of the fillers, the samples' linear and mass attenuation coefficient increases, which means an increase in the efficiency of the samples in X-ray attenuation. Generally, epoxy resin/PbO-NPs samples show a better effect than other samples. Therefore, these types of shields can attract more attention due to their lightness, cost-effectiveness, and far fewer environmental hazards than common lead shields.