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Tuberculosis (TB) caused by the bacterial pathogen <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of <i>Mtb</i> pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant <i>Mtb</i> strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers’ interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of <i>Mtb</i> pathogenesis and the importance of both natural and synthetic flavonoids against <i>Mtb</i> infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.