The EtOAc-soluble fraction from a methanolic extract of Hovenia dulcis Thunb. exhibited neuroprotective activity against glutamate-induced neurotoxicity in mouse hippocampal HT22 cells. The neuroprotective activity-guided isolation resulted in 8 phenolic compounds (1-8), such as vanillic acid (1), ferulic acid (2), 3,5-dihydroxystilbene (3), (+)-aromadendrin (4), methyl vanillate (5), (-)-catechin (6), 2,3,4-trihydrobenzoic acid (7), and (+)-afzelechin (8). Among these, compounds 6 and 8 had a neuroprotective effect on the glutamate-induced neurotoxicity in HT22 cells. Furthermore, compound 6 had a DPPH free radical scavenging effect with an IC50 value of 57.7 mu M, and a superoxide anion radical scavenging effect with an IC50 value of 8.0 mu M. Both compounds 6 and 8 had ABTS cation radical scavenging effects with IC50 values of 7.8 mu M and 23.7 mu M, respectively. These results suggest that compounds 6 and 8 could be neuroprotectants owing to their free radical scavenging activities.