This study described a new class of compounds — the indolcarboxamides — that could hold potential for the treatment of Mycobacterium tuberculosis. Two lead compounds, NITD-304 and NITD-349, were active against drug-sensitive and multidrug-resistant clinical isolates of M. tuberculosis and reduced infection in acute and chronic mouse models following oral administration. Mechanistic studies showed that the compounds target the trehalose monomycolate transporter MmpL3, which is essential for mycobacterial cell wall biosynthesis.