Twelve phenolic compounds were isolated from Thompson seedless grape and Grenache Noir (GN) wastes. These compounds were identified as quercetin 3-O-β-D-glucopyranosyl (1→2)-O-β-D-glucopyranoside, quercetin-3-O-α- L-rhamnopyranosyl (1→6)-O-β-D-glucopyranoside, quercetin-3-O-β-D-glucopyranoside, kaempferol-3-O-β-Dglucopyranoside, kaempferol-3-O-β-D-galactopyranoside, kaempferol-7-O-β-D-glucopyranoside, quercetin, catechin, isorhamnetin, gallic acid, cinnamic acid and ferulic acid. All structures were characterized by spectroscopic analyses and comparisons with the previously reported data. Two of the isolated compounds, gallic and catechin revealed a power full antioxidant activity which due to its hydroxyl groups. The present study has been designed also to explore the possible role of grape pomace extract against aluminium chloride-induced neurotoxicity in rats. Aluminium chloride (70 mg/kg) was administered daily for six weeks that significantly increased cognitive dysfunction and oxidative damage as indicated by a rise in nitrite oxide concentration. Chronic administration of grape pomace extract (13 and 129 mg/kg) daily to rats for a period of 6 weeks significantly improved the memory performance tasks of rats, attenuated oxidative stress (superoxide dismutase and catalase), decreased acetylcholinesterase activity. Results showed that BDNF, Bcl-2 and AChE return to their normal value after administration of the extract. This study demonstrated the neuroprotective potential of grape waste extract in aluminium chloride-induced cognitive dysfunction and oxidative damage.