Parkinson’s disease (PD) and related neurodegenerative diseases are among the fastest growing health concerns globally. At present, however, their increasing precedence has far outpaced the development of targeted therapeutics for these diseases. PD and other synucleinopathies are driven by the misfolding and aggregation of the intrinsically disordered 14 kDa protein α-synuclein in neurons, resulting in progressive neurodegeneration. As such, inhibition or modulation of a-synuclein aggregation dynamics is a promising therapeutic strategy for impeding disease progression and improving patient outcomes. Phenolic extracts from brewers spent grain, a waste product produced by the brewing industry, were obtained using conventional (NaOH) and deep eutectic solvents (choline chloride/maleic acid) to investigate its capability to modulate a-synuclein aggregation. Extracts displayed potent inhibition of fibril elongation in fluorescence kinetic assays, against both α-syn WT and disease-associated α-syn mutants (A53T and E46K), as well as decreasing monomer recruitment to fibrils. Fibrils formed in the presence of BSG extracts demonstrated altered fibril morphology when visualised via transmission electron microscopy, as well as decreased surface hydrophobicity of α-syn fibrils as measured via Nile Red fluorescence. Significanty, native cyclic ion-mobility mass spectrometry reveals significant structural heterogeneity of α-syn monomers, as well as extract-specific stabilisation of α-syn monomer conformations. Together, the data suggests significant conformational modulation of α-syn sturcture by BSG extracts which underlie mechanisms of inhibition, indicating these extracts to be a promising source of fibril-modulating lead compounds for therapeutic development for PD.