The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-α)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh5 (1) and vina-ginsenoside R25 (2), as well as eight known dammarane-type triterpene saponins, majonoside R2 (3), pseudo-ginsenoside RT4 (4), vinaginsenosides R1 (5), R2 (6), and R10 (7), ginsenosides Rg1 (8), Rh1 (9), and Rh4 (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb1, Rb2, Rc, Rd, and Re (12-16), were also identified in the extract. Among the compounds isolated, majonoside R2 (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalNfrNF-α-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.