We report here the effect of iridoid glucosides, isolated from Nyctanthes arbortristis, on redox homeostasis of Leishmania parasite. These compounds led to an increase in reactive oxygen species by inhibiting a crucial enzyme of redox metabolism of the parasite. Our experiments clearly showed that these compounds are highly active as antileishmanial agents. The in vitro experiments on intra-macrophageal amastigotes showed significant killing of parasite even at very low concentration. Determination of mechanism of action of iridoid glucosides showed that increased ROS level leads to oxidative stress, cell membrane damage and apoptosis of Leishmania sp. Our cellular toxicity assays on Human embryonic kidney (HEK 293) and mouse macrophage (J774A.1) cell lines showed these compounds to be very safe for therapeutics application.