Sixty-three extracts obtained from 18 plants traditionally used in the South Pacific archipelago Vanuatu for the treatment of infectious diseases were screened for antimicrobial and antiprotozoal activities. In addition, the extracts were subjected to a detailed analysis on cytotoxic effects toward a panel of human cancer cell lines, designed as a smaller version of the NCI60 screen. Intriguingly, 15 plant extracts exhibited strong cytotoxic effects specific for only one cancer cell line. Extracts of the leaves of Acalypha grandis Benth. significantly affected Plasmodium falciparum without showing obvious effects against the other protozoa tested. The leaves of Gyrocarpus americanus Jacq. displayed significant activity against Trypanosoma b. brucei and the leaves of Tabernaemontana pandacaqui Lam. I as well as the stems of Macropiper latifolium (L.f.) against Trypanosoma cruzi. In contrast none of the extracts showed relevant antibacterial or antifungal activity.