Tuberculosis (TB) is the number one cause of human death from infectious disease in the world. Current treatments are challenged by the high levels of drug-resistant Mtb infection, which including rifampicin-resistant TB (RR-TB), multidrug-resistant TB (MDR-TB), and extensively drug resistant TB (XDR-TB). New drugs with mechanism of action (MOA) are required for more effective treatments. The literature review covered TB disease, the discovery of current treatments and clinic candidates, natural products in TB drugs, two drug discovery strategies phenotypic based drug discovery (PDD) and target based drug discovery (TDD), and a platform to directly observe protein-ligand complexes. A combination of phenotypic screening with NMR fingerprints led to the isolation kokusaginine (2.1) from Flindersia maculosa Lindl. , a mixture of flindersiamine (2.2) and maculine (2.3) from Flindersia maculosa Lindl., fascaplysin (2.4) from Fascaplysinopsis sp., and agelasine D (2.5) from Agelas axifera. Fascaplysin (2.4) and agelasine D (2.5) showed strong inhibitory activities against M. smegmatis. Data analysis of phenotypic screening and molecular target screening prioritised four PFs fractions for identification of the active constituents. [...]