A deficiency in the human antioxidant system to scavenge free radicals results in mounting oxidative stress, causing various pathological conditions including immune system constraints. To support an underperforming antioxidant system and regulate homeostatic function, efficient and biocompatible reactive oxygen species (ROS) scavengers may be employed. At present, metal oxide-based antioxidants nanoparticles are of fundamental interest because of their smart surface property tailoring. A spray precipitation method was employed in this work to develop a strained and defect rich lanthanum oxide (La2O3) nanostructure. A contraction in d-spacing and distortion in planes and vacancies were observed in the nanostructure, causing microstrain as verified by the William-Hall uniform deformation model (UDM). Photocatalytic activity was evaluated against commercial La2O3 and Evonik Aeroxide TiO2 P25 via dye degradation experiments. A 30% degradation reduction confirmed the ability of the nanostructure to scavenge free radicals generated by P25 upon ultraviolet (UV) irradiation. Compared to the commercial La2O3, the nanostructured La2O3 showed an increase in UV absorption (200-400) nm due to a decrease in the optical band gap. A positive surface charge of the nanoparticles was observed from zeta potential measurements, suggesting sufficient colloidal stability. In vitro toxicity studies toward the nonmalignant human keratinocyte cell line (HaCaT) over a 24 h treatment period with the La2O3 nanoparticles exhibited no toxicity in comparison with the control and ZnO nanoparticles. The antioxidant properties of the nanoparticles were investigated by a dichlorofluorescein (DCF)-based assay which revealed a decrease in intracellular ROS in comparison with N-acetylcysteine (NAC) and H2O2. In addition, confocal microscopy imaging showed the internalization of the nanoparticles and subsequent DCF intensity change between the treated and untreated cells, as supported by flow cytometry analysis. Our findings suggest that defect-rich La2O3 nanoparticles could be used effectively as active inorganic UV filter and fluorescent contrast agent owing to their biocompatible antioxidant properties.