Advanced glycation endproducts (AGEs) are believed to be secondary factors in the selective neuronal injury associated with several neurodegenerative disorders. In this study, we investigated the protective effects of (−)-epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, against AGEs-induced damage in neuron cells. The results showed that EGCG treatment protected against glyceraldehyde-derived AGE-induced neurotoxicity, which is associated with an increase in intracellular reactive oxygen species, as well as against decreases in intracellular catalase (CAT) and superoxide dismutase (SOD) activities. EGCG treatment also decreased malondialdehyde and carbonyl levels, and AGEs formation. Treatment with 10 μM EGCG upregulated SOD and CAT levels, whereas glutathione peroxidase activity was reduced. Furthermore, 5 μM EGCG was found to down-regulate the mRNA level of the AGE receptor (RAGE) in neuronal cells up to 2.5 fold, as determined by real time PCR. The results demonstrated that EGCG may exhibit protective effects against AGEs-induced injury in neuronal cells through its antioxidative properties, as well as by interfering with AGEs-RAGE interaction mediated pathways, suggesting a beneficial role for this tea catechin against neurodegenerative diseases.