Tuberculosis (TB) is a contagious disease caused by the bacterium Mycobacterium tuberculosis, which most often affects the lungs, specifically pulmonary tuberculosis. One of the leading opportunistic diseases globally, affecting one-third population and resulting in approximately 1.5 million deaths annually. A weakened immune system against mycobacterial diseases has contributed to over 1.1 million people being co-infected with other life-threatening diseases, such as Human Immunodeficiency Virus (HIV). Abundant research highlighted the biotherapeutic potential of naturally occurring compounds against mycobacterial disorder. The increasing cases of MDR/XDR-TB are mainly derived from tuberculosis, coupled with the emergence of extensively drug-resistant (XDR) and multidrug resistance (MDR) strains, have made treatment more challenging. The condition emphasized the crucial requirement for novel plant-derived anti-TB medications. The persistence and latency of M. tuberculosis, along with drug resistance, have made tuberculosis treatment increasingly challenging. This review aims to comprehensively examine tuberculosis disease including current standard treatment, promising new drugs under development and the potential of medicinal plants and their bioactive compounds as alternative or supplementary therapies to combat mycobacterial infections, specifically focusing on the potential of plant-derived metabolites to act as effective antimycobaterial agents. It specifically highlights the role of plant-derived metabolites as effective antimycobacterial agents.