The increase of Plasmodial parasite resistance to available antimalarial drugs underscores the emergency to research alternatives to new drugs development. Medicinal plants traditionally used against malaria are potential source of new molecules; however, their efficiency must be scientifically validated. The present study is therefore aimed at evaluating the antiplasmodial potential and the cytotoxicity effect of alkaloids from Coffea Arabica and Coffea canephora. Alkaloids were extracted in acidic medium from powder of the dry leaves of each plant. Characterization of alkaloids was carried out using Mayer and Wagner reagents. Antiplasmodial tests based on the fluorescence of SYBR green were carried out on two isolates of Plasmodium falciparum. The revelation was made by flow cytometry. Toxicological evaluation of the extracts had been carried out through hemolysis test, erythrocyte sensitivity as well as cytotoxicity on Vero cells and Raw cells using spectrophotometry. Evaluation of antiplasmodial activity showed that C. arabica was active on isolates Pf3D7 and PfDd2 with resistance index of 0.78 and IC50 values of 9.53 ± 1.51 µg/mL and 7.48 ± 0.93 µg/mL respectively; On the other hand, C. canephora showed a weak activity on the strain Pf3D7 (IC 50 >100µg/mL) and a moderate activity on the strain PfDd2 (IC50 = 85.55 ± 1.17 µg/ mL). The toxicological profile was favorable for both extracts concerning hemolysis test (HC 50 >1000 µg/mL) and for cytotoxicity test (CC 50 >30 µg/mL). The present study revealed that these extracts could constitute glimmers of hope by offering an alternative to the management of malaria.