A series of new <i>N</i>-aryl galantamine analogues (<b>5a</b>-<b>5x</b>) were designed and synthesized by modification of galantamine, using Pd-catalyzed Buchwald-Hartwig cross-coupling reaction in good to excellent yields. The cholinesterase inhibitory and neuroprotective activities of <i>N</i>-aryl derivatives of galantamine were evaluated. Among the synthesized compounds, the 4-methoxylpyridine-galantamine derivative (<b>5q</b>) (IC<sub>50</sub> = 0.19 μM) exhibited excellent acetylcholinesterase inhibition activity, as well as significant neuroprotective effect against H<sub>2</sub>O<sub>2</sub>-induced injury in SH-SY5Y cells. Molecular docking, staining, and Western blotting analyses were performed to demonstrate the mechanism of action of <b>5q</b>. Derivative <b>5q</b> would be a promising multifunctional lead compound for the treatment of Alzheimer's disease.