A series of benzofuran piperidine derivatives were designed, synthesized and evaluated as multifunctional Aβ antiaggregant to treat Alzheimer's disease (AD). In vitro results revealed that all of them are very good Aβ antiaggregants and some of the compounds are potent acetylcholinesterase (AChE) inhibitors with moderate antioxidant property. Selected compounds were also tested for neuroprotection activity, LDH release, ATP production and inhibitory activity to prevent Aβ peptides binding to the cell membrane. The different modifications introduced in the structure of our lead compound 3 (hAChE IC<sub>50</sub> = 61 μM and self induced Aβ <sub>25-35</sub> aggregation 45.45%), to increase its activity toward AD related targets. The most interesting multifunctional Aβ antiaggregants were compounds 3a, 3h and 3i, highlighting 3h as potent Aβ antiaggregant and good antiacetylholinesterase inhibitor (self induced Aβ <sub>25-35</sub> aggregation 57.71% and hAChE IC<sub>50</sub> = 21 μM), with good neuroprotective and antioxidant activity. In addition, these three most promising compounds prevent intracellular reactive oxygen species (ROS) formation and cell apoptosis induced by Aβ<sub>25-35</sub> peptides in SH-SY5Y cells. Molecular docking studies were also accomplished to understand the binding interaction of these compounds on Aβ monomer, Aβ fibril and AChE. Based on all data, compounds 3a, 3h and 3i were concluded as potent multifunctional Aβ antiaggregant, useful candidate for the treatment of AD.