This study investigates the effect of phytochemical constituents from medicinally important plant Curcuma zedoaria (Christm.) Rosc., on hydrogen peroxide induced oxidative stress in mouse neuroblastoma-rat glioma hybridoma cells NG108-15. Phytochemical investigation of C. zedoaria rhizomes resulted in the isolation of nine sesquiterpenes (germacrone 1, dehydrocurdione 2, curcumenol 3, isoprocurcumenol 5, curcumenone 6, procurcumenol 7, zerumbone epoxide 8, zederone 9 and gweicurculactone 10) and one labdane diterpene (zerumin A 4). Curcumenol (3) and dehydrocurdione (2) showed 100% protection of the NG108-15 cells at the concentrations of 4 and 10μM, respectively. Procurcumenol (7), isoprocurcumenol (5), zerumbone epoxide (8), zerumin A (4) and germacrone (1) showed moderate activity (80-90% protection). In the oxygen radical antioxidant capacity (ORAC) assay, all the test compounds showed strong antioxidant activity except curcumenol (3) which showed moderate antioxidant activity, as compared to the reference standard quercetin.