A series of rasagiline-clorgyline hybrids was designed, synthesized and investigated in vitro for their inhibition of monoamine oxidase and amyloid-β aggregation. Most of compounds were found to be selective and highly potent hMAO-B inhibitors showing IC values in the nanomolar, and exhibited a moderate inhibition of amyloid-β aggregation. 7-((5-(methyl(prop-2-yn-1-yl)amino) pentyl)oxy)chroman-4-one (6j) was the most interesting compound identified in this research, endowed with higher hMAO-B potency (IC = 4 nM) and selectivity (SI > 25000) compared to the reference selective inhibitor rasagiline (IC = 141 nM, SI > 355), and exhibited good inhibitory activity against Aβ aggregation (40.78%, 25 μM). Kinetic and molecular modeling studies revealed that 6j was a competitive reversible inhibitor for hMAO-B. Moreover, compound 6j displayed low toxicity and good neuroprotective effects in SH-SY5Y cell assay, and could penetrate the blood-brain barrier according to the parallel artificial membrane permeability assay. Pharmacokinetics assay revealed that compound 6j possessed good pharmacokinetic profiles after intravenous and oral administrations. Overall, these results highlighted that compound 6j was an effective and promising multitarget agent against Alzheimer's disease.