A series of 7,8-dehydrorutaecarpine derivatives were synthesized and characterized as potential multifunctional agents for treatment of Alzheimer's disease (AD). All of these synthetic compounds showed high acetylcholinesterase (AChE) inhibitory activity with IC50 values ranged from 0.60 to 196.7 nM, and good selectivity for AChE over butyrylcholinesterase (BuChE) (125- to 3225-fold). A Lineweaver-Burk plot and molecular modeling study indicated these compounds could bind to both catalytic active site and the peripheral anionic site of AChE. Besides, compounds showed higher activity of inhibiting AChE-induced amyloid-beta (Aβ) aggregation than curcumin, higher anti-oxidative activity than Trolox, and could also be good metal chelators. Considering their low cytotoxicity, our results indicated that these derivatives provide good templates for developing new multifunctional agents for AD treatment.