Amyloid-β (Aβ) peptide instinctively aggregate and form plaques in the brain of Alzheimer's disease (AD) patients. At present, there is no cure or treatment for AD, and significant effort has, therefore, been made to discover potent drugs against AD. Previous studies reported that a resveratrol and clioquinol hybrid compound [()-5-(4-hydroxystyryl)quinolone-8-ol], , strongly inhibit Aβ aggregation and disassemble preformed fibrils. However, the atomic level details of the inhibitory mechanism of against Aβ aggregation and protrofibril disassembly remains elusive. In this regard, molecular docking and molecular dynamics (MD) simulation of Aβ monomer, Aβ monomer- complex, Aβ protofibril, and Aβ protofibril- complex were performed in the present study. MD simulations highlighted that bind in the central hydrophobic core (CHC) region, i.e., KLVFF (16-20) of Aβ monomer, which plays a critical role in Aβ aggregation. promote the formation of native helical conformation in the Aβ monomer and decrease the probability of D23-K28 salt bridge interaction that is critical in the formation of aggregation-prone β-sheet conformation. Further, destabilize Aβ protofibril structure by increasing the interchain distance between chains A-B, disrupting the salt-bridge interaction between D23-K28, and decreasing the number of backbone hydrogen bonds between chains A-B of the Aβ protofibril structure. The insights into the underlying inhibitory mechanism of small molecules that display potential anti-aggregation activity against Aβ will be beneficial for the rational design of more potent drug molecules against AD. Communicated by Ramaswamy H. Sarma.