The objective of this study is to evaluate the antimalarial property of Carica papaya L. leaf extracts and the cytotoxicity of active samples. C. papaya leaves were extracted and screened against Plasmodium falciparum 3D7 and Dd2 strains. Bioassay-guided fractionation was carried out. The dichloromethane extract of C. papaya leaves showed significant antiplasmodial activity against P. falciparum 3D7 and Dd2. Successful bioassay-guided fractionation afforded a fraction three to seven times more active than the dichloromethane extract. Carpaine was isolated from the most active alkaloidal extract and identified in the active fraction and dichloromethane leaf extract. The cytotoxicity of active samples was evaluated against NL20 cells. A haemolysis assay was performed on carpaine. Carpaine exhibited good activity against both strains of P. falciparum with IC₅₀ of 2.01 ± 0.18 μg/mL (4.21 μM) and 2.19 ± 0.60 μg/mL (4.57 μM) against 3D7 and Dd2 strains respectively. It exhibited high selectivity for the parasite and was non-toxic to healthy uninfected human red blood cells. This is the first study investigating the haemolysis potential of carpaine. The results provide a scientific basis for the traditional use of C. papaya leaves for malaria treatment. More work is required to evaluate the efficacy and safety of carpaine for further development into potential new antimalarial drugs.