The currently available anti-tuberculosis treatment (ATT) comprises exclusively of anti-bacterial drugs, is very lengthy, has adverse side effects on the host and leads to the generation of drug-resistant variants. Therefore, a combination therapy directed against the pathogen and the host is required to counter tuberculosis (TB). Here we demonstrate that -Gingerol, one of the most potent and pharmacologically active ingredients of ginger restricted mycobacterial growth inside the lungs, spleen and liver of mice infected with Mycobacterium tuberculosis (Mtb). The spleen of -Gingerol treated mice displayed increased expression of pro-inflammatory cytokines and enhanced Th1/Th17 responses confirming the immunomodulatory action of -Gingerol. Finally, -Gingerol displayed an excellent potential as an adjunct drug, along with front line anti-TB drug isoniazid. Interestingly, -Gingerol displayed stark anti-tubercular activity against dormant/starved bacilli and drug-resistant variants of Mtb. Taken together, these results indicate strong prospects of -Gingerol as an adjunct anti-mycobacterial and immunomodulatory drug for the treatment of drug-susceptible and drug-resistant strains of TB.Copyright © 2020 Elsevier B.V. All rights reserved.