To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of chalcone-O-carbamate derivatives was designed and synthesized based on the multitarget-directed ligands strategy. The in vitro biological activities were evaluated including AChE/BChE inhibition, MAO-A/MAO-B inhibition, antioxidant activities, Aβ aggregation inhibition, metal-chelating properties and neuroprotective effects against HO-induced PC12 cell injury. The results showed compounds 5b and 5h indicated highly selective BChE inhibitory activity with IC values of 3.1 μM and 1.2 μM, respectively and showed highly selective MAO-B inhibitory potency with IC values of 1.3 μM and 3.7 μM, respectively. In addition, compounds 5b and 5h could inhibit self-induced Aβ aggregation with 63.9% and 53.1% inhibition percent rate, respectively. Particularly, compound 5b was a potent antioxidant agent and neuroprotectant, as well as a selective metal chelator by chelating Cu and Al. Moreover, compound 5b could inhibit and disaggregate Cu-induced Aβ aggregation, which was further supported by the TEM images. Furthermore, compounds 5b and 5h could cross the blood-brain barrier (BBB) in vitro and conformed to the Lipinski's rule of five. Finally, the in vivo assay exhibited that compound 5b could improve scopolamine-induced cognitive impairment. Taken together, these results revealed that compound 5b might be a potential multifunctional agent for the treatment of AD, and deserved to do further structure optimization.