To investigate neuronal cell protective effects of an ethyl acetate fraction from chestnut inner skin, in vitro assays, including 2 0 ,7 0 -dichlorofluorescein diacetate, 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT), and lactate dehydrogenase (LDH), were performed. Intracellular accumulation of reactive oxygen species resulting from hydrogen peroxide (H2O2) treatment of PC12 cells was significantly reduced when ethyl acetate fractions were present in the medium compared to PC12 cells treated with H2O2 only. In a cell viability assay using MTT, the ethyl acetate fraction protected against H2O2-induced neurotoxicity, and inhibited LDH release into the medium. In addition, the ethyl acetate fraction improved in vivo cognitive ability against amyloid b-peptide (Ab)-induced neuronal deficit. High-performance liquid chromatography analyses showed that gallic acid, catechin, and epicatechin were predominant phenolics in the ethyl acetate fraction. Consequently, the results suggest that chestnut inner skin, including above phenolics, could ameliorate Ab-induced learning and memory deficiency, and be utilized as effective substances for neurodegenerative disorders, notably Alzheimer's disease.