In the present article a facile synthesis of cerium oxide nanoparticles (CNPs) encapsulated in PLGA microparticles is reported. The release kinetics of the CNPs from the PLGA matrix was investigated under acidic, basic and near-neutral pH. A diffusion model was applied to determine the diffusivity of the CNPs from the PLGA matrix. The morphology of the degraded PLGA particles was characterized by high resolution SEM. Superoxide dismutase (SOD) mimetic activity was retained in released CNPs for a longer period of time (∼90 days) under different pH. PLGA encapsulated CNP showed excellent biocompatibility. This study demonstrates a potential strategy to deliver CNPs using biodegradable PLGA that ensures a slow release of the CNPs over a long period of time. Thus, the synthesized PLGA encapsulated CNPs could find potential applications in tissue engineering like bone remodelling and regeneration, and protection from disorders caused by neurodegeneration.