A hallmark of mortality and morbidity, malaria is affecting nearly half of the world's population. Emergence of drug-resistant strains of malarial parasite prompts identification and evaluation of medicinal plants and their constituents that may hold the key to a new and effective anti-malarial drug. In this context, nineteen methanolic extracts from seventeen medicinal plants were evaluated for anti-plasmodial potential against Plasmodium falciparum strain 3D7 (Chloroquine (CQ) sensitive) and INDO (CQ resistant) using fluorescence based SYBR-Green assay and for cytotoxic effects against mammalian cell lines. Leaf extract of two plants showed promising in vitro anti-malarial activity (Pf3D7 IC ≤ 10 μg/ml); one plant extract showed good activity (Pf3D7 IC = 10.1-20 μg/ml); seven were moderately active (IC = 20.1-50 μg/ml), four plant extracts showed poor activity (PfD7 IC = 50.1-100 μg/ml) and five extracts showed no activity up to IC = 100 μg/ml. Further, six extracts were found equipotent to PfINDO (resistance index ranging 0.4-2) and relatively nontoxic to mammalian cell lines HEK293 (cytotoxicity index ranging 1.4-12.5). Based on good resistance and selectivity indices, three extracts were evaluated for in vivo activity in Plasmodium berghei ANKA infected mice at a dose of 500 mg/kg and they showed significant suppression of P. berghei parasitemia. Further, these active plant extracts were fractionated using silica-gel chromatography and their fractions were evaluated for anti-plasmodial action. Obtained fractions showed enrichment in antimalarial activity. Active fractions were analyzed by gas chromatography and mass-spectrometery. Results suggests that the three active plant extracts could serve as potent source of anti-malarial agent and therefore require further analysis.