In the central nervous system (CNS), extra virgin olive oil (EVOO) produces interesting effects against neurodegenerative disorders including Alzheimer's disease (AD). The valuable properties of EVOO are largely ascribed to oleuropein aglycone (OA), its most abundant phenolic constituent. In particular, it has been demonstrated that in AD, OA produces strong neuroprotective effects being able to reduce amyloid ß (Aß) aggregates, thereby diminishing the related cytotoxicity and inflammation. OA prevents Aß aggregation, but more importantly OA was able to disrupt the preformed Aß fibrils. Herein, we describe a comprehensive computational investigation of the mechanism of action of OA as an Aß fibril disruptor at the molecular level. We employed extensive molecular docking calculations and long-time molecular dynamics simulation for mimicking the system of OA/Aß fibrils. The results showed that OA is able to move in depth within the Aß fibrils targeting a key motif in Aß peptide, known to be relevant for stabilizing the assembled fibrils. OA causes a structural instability of preformed Aß fibrils, determining the effective Aß fibril disaggregation. Accordingly, this study highlighted the role of OA as a potent anti-amyloidogenic drug. On the other hand, our work has relevant implications for rationally designing potent multifunctional compounds acting as disease modifying anti-Alzheimer's drugs for the development of innovative anti-AD therapeutics.