EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. The polyphenol (-)-epigallocatechin gallate (EGCG), found in green tea, inhibits α-synuclein and amyloid-β fibrillogenesis by binding to natively unfolded polypeptides and promoting the self-assembly of unstructured oligomers. This study shows that EGCG can convert large, mature α-synuclein and amyloid-β fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells. Mechanistic studies reveal that EGCG directly binds to β-sheet-rich aggregates and mediates conformational changes without disassembling them into monomers or small diffusible oligomers. These findings suggest that EGCG is a potent remodeling agent of mature amyloid fibrils. EGCG was shown to remodel preformed amyloid aggregates by binding to β-sheet-rich structures and altering their conformation. This process was confirmed using biochemical and biophysical assays, as well as cell-based experiments. EGCG treatment reduced the toxicity of α-synuclein and amyloid-β aggregates in cell models, indicating that it may be a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's and Parkinson's. EGCG was also shown to remodel amyloid-β fibrils and oligomers into benign SDS-resistant structures, reducing their toxicity in cell-based assays. The study suggests that EGCG binds to preformed amyloid fibrils and directly alters their morphology in vitro and in vivo. The results indicate that EGCG may be a model substance for potential therapeutics for systemic and neurodegenerative amyloid diseases.EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. The polyphenol (-)-epigallocatechin gallate (EGCG), found in green tea, inhibits α-synuclein and amyloid-β fibrillogenesis by binding to natively unfolded polypeptides and promoting the self-assembly of unstructured oligomers. This study shows that EGCG can convert large, mature α-synuclein and amyloid-β fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells. Mechanistic studies reveal that EGCG directly binds to β-sheet-rich aggregates and mediates conformational changes without disassembling them into monomers or small diffusible oligomers. These findings suggest that EGCG is a potent remodeling agent of mature amyloid fibrils. EGCG was shown to remodel preformed amyloid aggregates by binding to β-sheet-rich structures and altering their conformation. This process was confirmed using biochemical and biophysical assays, as well as cell-based experiments. EGCG treatment reduced the toxicity of α-synuclein and amyloid-β aggregates in cell models, indicating that it may be a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's and Parkinson's. EGCG was also shown to remodel amyloid-β fibrils and oligomers into benign SDS-resistant structures, reducing their toxicity in cell-based assays. The study suggests that EGCG binds to preformed amyloid fibrils and directly alters their morphology in vitro and in vivo. The results indicate that EGCG may be a model substance for potential therapeutics for systemic and neurodegenerative amyloid diseases.