This study was led with the aim of providing original antimalarial agents to thwart the parasite drug resistance. Plants not yet explored phytochemically provide a good source of candidates. Reunion flora possesses up to 30% endemic vegetation. Therefore, 9 plants from this island selected using ethnopharmacology and chemotaxonomy, were investigated for their potential and specific antimalarial activities. Plant extracts were prepared by maceration using CH2Cl2 and MeOH and tested for in vitro activity against 3D7 and W2 strain of Plasmodium falciparum. The most active extracts were then tested for in vitro cytotoxicity on human WI-38 cells to determine the selectivity index. Those extracts were also investigated against P. berghei infecting mice, based on the 4-day suppressive test of Peters [1]. The dichloromethane leaves extracts from Nuxia verticillata Lam., Psiadia arguta Voigt., Lantana camara L. and the methanol bark extract from Aphloia theiformis (Vahl) Benn bark, and Terminalia bentzoe L. leaves displaying in vitro IC50 values ranging from 5.7 to 13.3µg/ml were the most active. Extracts from Psiadia, Aphloia and Teminalia exhibited also significative parasite inhibition in vivo: 75.5%, 65.6% and 83.5%, respectively. In the end, 2 plants showed interesting antimalarial activity with good selectivity: Aphloia theiformis (Vahl) Benn. (Aphloiaceae) and Terminalia bentzoe L. (Combretaceae). Nuxia verticillata Lam. (Buddlejaceae) still need to be tested in vivo, with new plant material. Later on, bioguided chromatographic fractionation will be used to isolate the compounds responsible for the activity.