Neuron apoptosis induced by β-amyloid (Aβ) is an important precipitating factor in the pathogenesis of Alzheimer's disease (AD). In the present study, the effects of piceatannol (PT) and pterostilbene (PS) against Aβ-induced apoptosis in PC12 cells were evaluated. PT and PS both showed observable anti-apoptosis activity. Increased cell viability, decreased apoptosis rate and declining intracellular ROS were observed after PT and PS treatment. For the signaling pathway, PT significantly promoted phosphorylation of Akt and Bad, further suppressed Bcl-2/Bax expression and inhibited cleavage of caspase-9, caspase-3 and PARP. PS promoted phosphorylation of Akt without affecting the other factors. The experimental results, for the first time, unambiguously suggested that PT showed a comprehensive protective effect against Aβ-induced apoptosis in PC12 cells via a novel PI3K/Akt/Bad signaling pathway and downstream mitochondria-mediated and caspase-dependent signaling pathway. Unlike PT, PS inhibited apoptosis against Aβ through a different PI3K/Akt signaling pathway in which the downstream targets need to be further investigated. The results also provide the basis for dietary intervention involved in the prevention and adjunctive therapy of AD.