We conducted a phase I trial of Gynostemma pentaphyllum, grown in northern Thailand, to evaluate its safety in three groups of healthy volunteers. Fourteen, fifteen and fourteen volunteers respectively received the water extract of G. pentaphyllum in capsules at the doses of 50, 200 and 400 mg twice daily for two months. There were no major adverse events reported from any of the three groups throughout the study. Significant changes in hematological parameters, natural killer cell activities and the numbers of CD3+, CD4+ and CD8+ cells were not seen during taking the extract. Some biochemical parameters were significantly different from baseline data. Those values were, however, within normal limits and did not result in clinically significant conditions. Our results suggested that the water extract of G. pentaphyllum at the doses of 50, 200 or 400 mg twice daily given to healthy volunteers for two months was safe.