Leishmania is a unicellular protozoan parasite causing a wide range of human diseases ranging from localized self-healing cutaneous lesions to fatal visceral infections.The aim of the present study is to assess the cytotoxic, anti-proliferative, and apoptotic effects of oleuropein on Leishmania major promastigotes (MHOM/SA/84/JISH) and to compare its effects with the reference drug sodium stibogluconate (pentostam).Cytotoxicity and promastigote proliferation were measured using MTT colorimetric assay. Furthermore, the Annexin V/propidium iodide staining technique followed by flow cytometry was used for studying the cell death properties of oleuropein.In the present report we have shown that oleuropein, a pharmacologically safe, natural product of olive leaf, has a potent leishmanicidal effect. Indeed, oleuropein exhibits cytotoxic and anti-proliferative effects against Leishmania major promastigotes. Moreover, oleuropein triggers death through apoptosis, whereas pentostam induces death mainly via necrosis on Leishmania major promastigotes.Here we demonstrate for the first time that the non-toxic, natural product oleuropein has apoptotic properties against Leishmania major promastigotes. Further studies are needed to investigate its molecular pathway.