The trypanocidal potential of the natural chalcone flavokawin B, which was isolated from the hexanic extract of Wedd., is reported here. Although flavokawin B is widespread, this is the first report about its trypanocidal properties on both (IC = 9.5 µM, IC = 34.7 µM benznidazol, Y strain) epimastigotes and (IC = 4.8 µM, IC = 6.4 µM pentamidine, 29-13 strain) procyclic forms, which was also corroborated on strain 427 (IC = 6.2 µM). In order to learn more about its properties, unspecific cytotoxicity on Hep G2 cells was investigated as well as the -splicing inhibitory potential on cells. The results shown here point to flavokawin B as a candidate in the search for new agents. It is also cheaper and less toxic than the available drugs to treat trypanosomiasis with a special focus on sleeping sickness disease.