Aggregation of misfolded amyloid beta (A) peptides into neurotoxic oligomers and fibrils has been implicated as a key event in the etiopathogenesis of Alzheimer’s disease (AD). Ginnalin A (GA), a polyphenolic compound isolated from the red maple (), has been found to possess anticancer, anti-glycation, and anti-oxidation properties. Using thioflavin-T (ThT) fluorescence, surface plasmon resonance (SPR), and atomic force microscopy (AFM), we demonstrate that GA can also effectively inhibit A aggregation by primarily binding to A monomers in a dose-dependent manner. Furthermore, GA can bind to multiple sites of A aggregates to disassemble preformed fibrils and convert them into small aggregates. Circular dichroism (CD) spectra showed that these small aggregates are much less abundant in -sheets, while cell viability assay confirms that they are essentially innocuous. Molecular dynamics (MD) simulations revealed that GA preferentially contacts with the C- and N-terminal -sheets and the U-turn region of A(1-42) oligomers through hydrophobic interactions and hydrogen bonding. Compared with other natural compounds that have shown promise in anti-A fibrillogenesis and ameliorating A-induced cytotoxicity, GA is unique in that it exhibits a more efficient inhibition of A aggregation at the very early stage through its strong interaction with A monomers and exerts its inhibitory effect at a lower dosage.