The eye lens is rich in proteins called crystallins, whose native conformation is crucial for preserving its transparency. With aging, crystallins may be exposed to environmental changes, which could lead to their aggregation and eventually to cataract development. Human γD-crystallin, among the most abundantly expressed γ-crystallins in the lens, was shown to form amyloid aggregates under denaturing conditions in vitro. However, the exact mechanism of aggregation remains to be clearly defined. Here, using prediction algorithms and biophysical methods, we identified a?hexapeptide?41GCWMLY46?as a most aggregative fragment in human γD-crystallin. Two aromatic?naphthoquinone-tryptophan?hybrid molecules (NQTrp and Cl-NQTrp),?inhibited?the in vitro aggregation of this?hexapeptide?as well as?full-length?γD-crystallin in a dose-dependent manner, plausibly facilitated by hydrogen bonding and aromatic contacts with the hydrophobic residues. The two compounds had no toxic effect toward retinal cell culture and reduced the cytotoxicity induced by aggregates of the?hexapeptide. In addition, NQTrp and Cl-NQTrp were able to disassemble pre-formed aggregates of the?hexapeptide?and the?full-length?γD-crystallin. Our results indicate that the?amyloidogenic?hexapeptide?is a useful?model?for screening inhibitors of γD-crystallin and that the NQTrp hybrid scaffolds may serve as leads for developing new drugs for treating cataract.