The methanol fraction of an ethanolic extract from the roots of Polygala tenuifolia Willd. showed antagonistic action on neurotoxicity induced by glutamate and serum deficiency in PC12 cells. Bioassay-guided fractionation led to the isolation of six new triterpenoid saponins, onjisaponins V - Z, and Vg ( 1 - 6), together with ten known saponins ( 7 - 16). The structures of 1 - 6 were elucidated by spectroscopic and chemical methods. Screening results indicated that compounds 1 - 16 showed neuroprotective effects against serum deficiency and glutamate at the concentration of 10 (-5) mol/L.