Aggregation and deposition of beta-amyloid peptides (Aβ), a pathological hallmark of Alzheimer's disease, has been recognized as a potent activator of neuroinflammation and neuronal dysfunction. In this study, the underlying molecular mechanisms responsible for the neuroprotective effects of corilagin against Aβ25-35-triggered neurotoxicity and inflammatory responses were investigated in PC12 cells. Pretreatment with corilagin effectively protected PC12 cells against Aβ25-35-induced damage and apoptosis. Aβ25-35 induced damage in PC12 cells as revealed by increased production of reactive oxygen species, caspase-3 activity, and cell cycle arrest was attenuated by corilagin pretreatment. Corilagin not only significantly suppressed the production of neurotoxic inflammatory mediators such as tumor necrosis factor-α, nitric oxide, and prostaglandin E2 but also downregulated cyclooxygenase-2 and inducible nitric oxide synthase expression in PC12 cells. It also exerted a beneficial effect by suppressing the degradation of inhibitor of κB (IκB)-α and subsequent activation of transcription factor nuclear factor κB (NF-κB), mostly through inhibition of extracellular signal-regulated kinase activity in comparison to c-Jun N-terminal kinase and p38 MAP kinase (p38) mitogen-activated protein kinase activity. These findings suggest that attenuation of Aβ25-35-induced inflammatory responses by downregulating the NF-κB signaling pathway might be a valuable strategy for both Alzheimer's disease prevention and/or treatment.