We report for the first time a novel series of tellurides bearing sulfonamide as selective and potent inhibitors of the β-class carbonic anhydrase (CA; EC 4.2.1.1) enzyme expressed in <i>Leishmania donovani</i> protozoa. Such derivatives showed high activity against axenic amastigotes, and among them, compound <b>5g</b> (4-(((3,4,5-trimethoxyphenyl)tellanyl)methyl)benzenesulfonamide) showed an IC<sub>50</sub> of 0.02 μM being highly selective for the parasites over THP-1 cells with a selectivity index of 300. The in vitro and in vivo toxicity experiments showed compound <b>5g</b> to possess a safe profile and thus paving the way for tellurium-containing compounds as novel drug entities.