Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major component of the plaques, amyloid-β (Aβ), is generated from amyloid-β precursor protein (APP) by β- and γ-secretase-mediated cleavages. Multiple lines of evidence demonstrate that overproduction/accumulation of Aβ in vulnerable brain regions is a primary cause of the pathogenesis of AD. Among the twelve polyphenols isolated from the leaf extracts of Vitis thunbergii var. taiwaniana (VTT), stenophyllol C, stenophyllol B, ampelopsin C, vitisin A, and davidiol A were shown to significantly reduce both Aβ40 and Aβ42 levels in N2a695 cells. Further studies revealed that ampelopsin C and vitisin A reduce Aβ production through inhibiting β-secretase activity, while the effects of the other active polyphenols on reducing Aβ generation are through different mechanisms. These results suggest that VTT extracts may be beneficial for AD prevention and treatment.