The discovery of new antimalarial drugs from medicinal plants is urgently neededdue to the development of multidrug-resistant Plasmodium falciparum. Therefore, Piper sarmentosum(kaduk), a commonly used as a herbal medicine to treat malarial symptoms was screened for antimalarial as well as toxicological activities of their methanol and water leaves extracts. The inhibitory concentration (IC50) of P. sarmentosum methanol and water extracts against a chloroquine-sensitive strain (3D7) of P. falciparumwas determined by using a malarial SYBR Green I-based fluorescence (MSF) assay. The lethal concentration (LC50) of the plant extracts was evaluated by using a brine shrimp lethality test (BSLT). The presence of heavy metal contents in the crude extract was alsodetected by using an atomic absorption spectrometry (AAS). Both methanol and water extracts showed an inactive antimalarial activity with an IC50value of 138.8 ± 0.122 μg/mL and 229.7 ± 0.125 μg/mL, respectively. The water extract was considered non-toxic (LC50= 2741.7 3.16 ppm), while the methanol extract was toxic (LC50= 894.94 0.018 ppm). The heavy metals such as plumbum (Pb), zinc (Zn), cadmium (Cd) and chromium (Cr) were identified in the crude extract but they were below the safety limits recommended except for arsenic (As). Further investigations are required to determine the toxicological profiles of P. sarmentosum extracts on mammalian models.