The emergence and treatment of Drug resistant Tuberculosis (DRTB) have become a global health issue. Herbal drugs promises other possible options for Tuberculosis treatment.. In the current study, anti-mycobacterial activity of Piper longum, Cressa cretica and Calotropis gigantea extracts were tested. The methanolic extract of these plants was screened against H37Rv strain using MGIT BACTEC 960 system. The extracts showed inhibitory activity against Mycobacterium tuberculosis H37Rv strain. Piper longum and Cressa cretica showed inhibition at 125µg/mL and Calotropis gigantea at 250µg/mL. However, isoniazid and Rifampicin as standard showed higher inhibitory activity against M. tuberculosis respectively at 0.05µg/mL and 0.12µg/mL when compared to the crude extract. The present study demonstrates the anti-tubercular potential of Piper longum and Cressa cretica as a new anti-mycobacterial agent. Although, the action of these compounds and their active principles require further purification and molecular characterization besides in vivo testing to evaluate their capacity as novel anti-TB agents.