The anti-leishmanial activity of plant derived natural products has been illustrated.Due to the growing unresponsiveness to conventional therapy search for new anti-leishmanial compounds continues. The anti-leishmanial activity as well as underlying mechanism of action of plant derived natural products; particularly Malabaricones from Myristica malabarica, ethanolic extracts of Piper betle and Artemisinin derived from Artemisia annua have been studied. For Artemisinin, major role is played by labile iron pool in free radical generation culminating in apoptosis of Leishmania parasites whereas in infected macrophages it up regulated NO production and iNOS levels back to baseline levels which was corroborated by in vivo experiments wherein L. donovani infected mice treated with Artemisinin showed a sustained increase in Th1 (IFN-Gamma and IL-2) cytokines; collectively, artemisinin and its analogs are leishmanicidal agents, whose action is mediated via both a pro-oxidant activity upon parasites and an immunomodulatory action upon macrophages in a mouse model of visceral leishmaniasis