Majonoside-R2 (MR2), an ocotillol-type saponin, is a dominant saponin component of Vietnamese ginseng. We have investigated the effect of MR2 on behavioral and pathophysiological changes caused by psychological stress such as the communication box paradigm-induced psychological stress (CBP stress), conditioned fear stress and social isolation stress in laboratory animals, and elucidated the possible neuronal mechanisms underlying the action of this compound. MR2 attenuated CBP stress- and conditioned fear stress-induced antinociception, had a protective effect against CBP stress-induced gastric lesions, and restored the hypnotic activity of pentobarbital decreased by CBP stress or social isolation stress to the level of the unstressed controls. Accumulating evidence strongly suggests the involvement of the central opioid, GABAA receptor and corticotropin-releasing factor mechanisms in the effect of MR2. Here we review the antistress effect of Vietnamese ginseng, especially focusing on the effect of MR2 on psychosomatic disorders caused by psychological stress.