Background: Previous studies have shown the cognitive effect of the embryo of Nelumbo nucifera on scopolamine-induced memory impairment and neuroprotective effect against glutamate-injured neurotoxicity in HT-22 cells. Objectives: The present study was designed for the purpose of evaluating the neuroprotective activity of compounds isolated from the embryo of N. nucifera seeds on glutamate-induced cell death in HT-22 cells. Materials and Methods: We isolated compound from the embryo of N. nucifera using various chromatograms and confirmed chemical structure by various spectroscopy. The neuroprotective effects of the compounds against glutamate-induced cell death in HT-22 cells were investigated using an (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: We isolated 6 compounds, 1,2,3,4-tetrahydro-7,8-isoquinolinediol (1), 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl) methyl]-2-methyl-6,7-Isoquinoline diol (2), 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl) methyl]-2-methyl -7-Isoquinolinol(3),1-(3,4,5-trihydroxyphenyl)-ethanone(4), 1-(2,3,5,6-tetrahydroxyphenyl)-ethanone(5),3-(prop-1-enyl) benzene-1,2,4,5-tetrol (6) from the embryo of N. nucifera . Among these compounds, 1,2,3,4-tetrahydro-7,8-isoquinolinediol and 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-2-methyl-6,7-Isoquino linediol significantly decreased glutamate-induced cell death in HT-22 cells. In addition, these compounds exacerbated the reactive oxygen species level and intracellular Ca2+ accumulation. Conclusion: The neuroprotective efficacy of 1,2,3,4-tetrahydro-7,8-isoquinolinediol and 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl) methyl]-2-methyl-6,7-Isoquinolinediolmay be related to their antioxidative effect.