Localized oxidative stress plays a key role in the development of retinal degenerative diseases, with diabetic retinopathy (DR) being one of them, contributing significantly to this vision-threatening complication of diabetes. Increased oxidative burden leads to dysfunction across various retinal cell types, including vascular endothelial cells, neurons, glial cells and pericytes. Importantly, even after achieving normalized glycemia, the detrimental effects of oxidative stress persist. Nonetheless, growing data highlights the therapeutic potential of antioxidants in safeguarding vision. However, extensive clinical trials using traditional antioxidants have produced mixed results. Therefore, probucol, known for its ability to limit vascular oxidative stress, decrease superoxide generation, and improve endogenous antioxidant activity, is a promising candidate explored in this review. In addition to describing probucol, this review will explore novel therapeutic formulation strategies by incorporating bile acid into probucol-loaded nanoparticles to enhance drug delivery to the posterior segment of the eye for more effective management of DR. The integration of bio-nanotechnology with probucol and bile acids represents a promising avenue for developing effective therapies for DR, addressing the limitations of traditional antioxidant treatments.