Four new dihydropyranocoumarins were isolated from Angelica gigas roots through neuroprotective activity-guided isolation and were characterized as decursinol derivatives 4"-hydroxytigloyldecursinol (1), 4"-hydroxydecursin (2), (2"S,3"S)-epoxyangeloyldecursinol (3), and (2"R,3"R)-epoxyangeloyldecursinol (4), respectively. All four new dihydropyranocoumarins and major coumarin derivatives of A. gigas, decursinol and decursin, exhibited significant protective activity against glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells at concentrations ranging from 0.1 to 10 microM.