As oxidative stress is involved with inflammation and neovascularization, blocking oxidative stress may be beneficial for reducing inflammation. To investigate the potential use of cerium oxide nanoparticles (CeNPs) in treating neovascularization-related ophthalmic diseases, various CeNP samples were synthesized, and the sample with the best antioxidant efficacy was used in a rat model of inflammation-associated corneal neovascularization. This synthesized cerium oxide showed good biocompatibility and was capable of mediating a decrease in the expression levels of inflammatory factors via antioxidative stress. Additionally, in vitro tests showed that the Ce3+/Ce4+ ratio of the CeNPs directly affected the antioxidative activity, with higher ratios achieving better efficacy. The anti-inflammatory efficacy of the functional CeNPs was examined both in vitro and in vivo. Slit-lamp biomicroscopy and histological analysis revealed the gradual development of corneal neovascularization, suggesting that inflammation and neovascularization could be controlled by reducing the level of oxidative stress. CeNP-induced antioxidation could serve as a new strategy in the development of long-acting functional agents for treating ophthalmic diseases.