AbstractA series of (E)‐2‐((1H‐imidazol‐1‐yl)methyl)‐2‐((benzyloxy)methyl)‐2,3‐dihydro‐1H‐inden‐1‐one O‐benzyl oximes (6a‐j) were prepared and evaluated for their in vitro antileishmanial potency against Leishmania donovani (in promastigote and amastigote models). At a concentration of 05‐μg/mL, compounds 3a‐d, 4a‐d, 5a, 5b, 6a‐d, and 7a‐d exhibited 97% to 100% and 87% to 100% inhibition against promastigotes and amastigotes, respectively. Compounds 6a, 6d‐6j and 6a, 6i, 6j exhibited equal antileishmanial potency to that of SSG and Pentamidin at lower values of IC50.