Schinus terebinthifolius is a medicinal plant with biological in vitro activity against clinically relevant parasites such as Leishmania amazonensis and L. chagasi. Considering its antiparasitic activity, this work aimed to investigate the in vitro effects of S. terebinthifolius fractions against P. falciparum using SYBR fluorescence tests, its cytotoxicity towards monkey kidney cells and efficacy against malaria in a murine model of P. berghei infection. For the first time, screening results with several extracts and fractions are reported herein. Five out of 16 fractions obtained from leaves, flowers, unripe and ripe berries with dichloromethane, ethyl acetate and butanol solvents used in plant extraction were active against P. falciparum. Two ethyl acetate fractions with no cytotoxicity in vitro presenting selectivity indexes of ≥111 and ≥167 exhibited no antimalarial activity in mice at 500 mg/kg. Preliminary LCMS analysis of the ethyl acetate subfractions showed antiplasmodial effect in vitro with high specific index suggesting that such activity is related to polyphenolics in the fractions, mainly flavonoids. Additional studies should be undertaken to identify the compound(s) with anti-malaria activity.