Cerium oxide nanoparticles (CeO2-NPs) have suggested promising advantages in semiconductors and biomedical applications due to the provided optical, electrical, antioxidant, and antibacterial activity. However, the widely reported synthetic strategies for CeO2-NPs demand toxic precursors and intermediary pollutants that represent a severe limitation in CeO2-NPs applications. Therefore, it is required to develop greener strategies that implicate ecological precursors to reduce the negative impact on the scalability of CeO2-NPs. In this regard, we applied Lycium cooperi (L. cooperi) aqueous extracts as an unexplored potential green reducing agent for the eco-friendly synthesis of CeO2-NPs. The L. cooperi extract showed the presence of alkaloids, flavonoids, cardiac glycosides, and carbohydrate-derived families that were assessed for spherical monodispersed CeO2-NPs under a rapid chemical reduction. Moreover, the elemental composition displayed Ce and O, indicating a high pure CeO2-NPs characterized by an interplanar cubic crystalline structure. Furthermore, we detected the presence of stabilizing functional groups from L. cooperi, which after a controlled annealing process, resulted in a band gap energy of 3.9 eV, which was optimal for CeO2-NPs. Thus, the results proposed L. cooperi as an environmentally friendly synthesis method that can open a new route for CeO2-NPs in biomedical and industrial applications.