The aggregation of crystallin proteins is related to cataracts and age-related macular degeneration. Apart from surgical replacement of the cataract lens, no other alternative treatment is available till date for this ailment. In the current work, we carried out an in-depth investigation of the effect of polyphenol-loaded nano-formulations on the aggregation of γD-crystallin. At first, the protein was allowed to form amorphous aggregates under denaturing conditions. Several polyphenols were then tried to inhibit the aggregation of the protein. Among the polyphenols tested, resveratrol and quercetin were found to be the most effective. Since polyphenols are prone to degradation, they were encapsulated in chitosan nanoparticles in order to provide ambient conditions for them to function effectively. The loading efficiency and polyphenol release kinetics were subsequently tested. Finally, the efficacy of resveratrol/quercetin-loaded chitosan nano-particles as inhibitors of γD-crystallin aggregation was confirmed in a series of experiments demonstrating the potency of the system in the prospective therapeutic intervention of eye ailments concerning self-assembly of γD-crystallin proteins.