A series of coumarin derivatives were designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease (AD). In vitro studies showed that most of these compounds exhibited significant potency to inhibit hMAO-B selectively and self-induced Aβ1-42 aggregation. In particular, compound 13 presented the greatest potential to inhibit hMAO-B (IC50=0.081μM, SI >1234) and good inhibition of Aβ1-42 aggregation (52.9% at 20μM). Moreover, compound 13 could function as a metal-chelator, penetrate the blood-brain barrier (BBB) and show low cell toxicity in rat pheochromocytoma (PC12) and SH-SY5Y cells. Taken together, these results suggested that compound 13 might be a promising multifunctional agent for AD treatment.