Visceral Leishmaniasis (VL), a deadly form of leishmaniasis caused by Leishmania donovani, is one of the most serious threats yet neglected complication and a major arena of research of the 21st century. Phyto-extracts are the major source of anti-microbial agent, responsible for killing many intracellular and extracellular microbes. These therapeutic benefits are caused by increased nitrite generation, activation of Th1 cytokine response, elevated serum chemokines and induction of reactive oxygen species. Our review highlights the important contributions of several phyto-products like artemisinin, glycyrrhizic acid, quassin, and resveratrol which have shown to be efficient against the progression and establishment of L. donovani infection. Therefore, the present study deals with a detailed account of the potentiality of immuno modulators, especially these four most widely recommended anti-leishmanial phyto-agents that gained momentum in the 21st century, including the way they carry out their mechanistic roles in parasite clearance and host healing.