Based on an ethnobotanical survey, 41 Guinean plant species widely used in the traditional treatment of fever and/or malaria were collected. From these, 74 polar and apolar extracts were prepared and tested for their in vitro antiprotozoal activity along with their cytotoxicity on MRC-5 cells. A potent activity (IC50 < 5 µg/mL) was observed for Terminalia albida, Vismia guineensis, Spondias mombin, and Pavetta crassipes against Plasmodium falciparum; for Pavetta crassipes, Vismia guineensis, Guiera senegalensis, Spondias mombin, Terminalia macroptera, and Combretum glutinosum against Trypanosoma brucei brucei; for Bridelia ferruginea, G. senegalensis, V. guineensis, P. crassipes, and C. glutinosum against Trypanosoma cruzi. Only the extract of Tetracera alnifolia showed a good activity (IC50 8.1 µg/mL) against Leishmania infantum. The selectivity index of the active samples varied from 0.08 to > 100. These results may validate at least in part the traditional use of some of the plant species.