This research tested a nanoparticle biomaterial in improving diabetic retinopathy (DR). Poly(lactic co glycolic acid) (PLGA)-CeO2, composed of cerium oxide (CeO2) and PLGA, was chosen as the new nanocomposite for DR treatment. DR mouse models were constructed to test the anti-DR efficiency of polyethylenimine (PEI)-CeO2 and PLGA-CeO2. The infiltration efficiency test was conducted to study the transport performance of the delivery system, and the clinical effect of CeO2 was observed regarding the structural integrity, oxidative stress response, inflammatory reaction, and retinal ganglion cell (RGC) apoptosis in the retina tissue. We observed that the infiltration efficiency of PLGA-CeO2 was higher than that of PEI-CeO2, and PLGA-CeO2 could inhibit oxidative stress and inflammatory reaction. Furthermore, the clinical efficacy of PLGA-CeO2 in rescuing amotio retinae and reducing RGC apoptosis was superior to PEI-CeO2. Conclusively, PLGA-CeO2 has a significant capacity for antioxidation and reducing RGC apoptosis in mouse models, which can be a potential compound nanodrug for DR treatment in the future.