Mycobacterium species are among the most dangerous group of pathogens which have a broad host and disease spectrum. They are resistant to multiple drugs and respond to complex drug therapy, which is also being failed to control them. Vaccination of Mycobacterium is being done for a long period globally for the prevention of diseases of Mycobacterium. Various types of vaccines are being used, but vaccine failure, lower efficacy, and secondary issues lead to limiting their use. These situations demand researching proper safe control, which may help counter the diseases and issues related to Mycobacterium. Multiple therapies are being suggested, but the botanicals remain promising for their control. The therapies to be developed are supposed to have direct antimycobacterial actions like they may target its cell wall, cell membranes, protein synthesis or DNA gyrase activity, and DNA assembly. Botanicals found in plants have been found to possess these activities in the research. Researchers claim direct and indirect activities of botanical compounds and claim that botanicals can be effective for proper control of Mycobacterium spp. Although research claims that botanical compounds can control Mycobacterium spp. but there is a need to search their pharmacological interactions, long-term use effects, toxic reactions, and efficacy to treat real-world challenges. This review highlights the diseases cause by Mycobacterium spp., the identification of Mycobacterium spp., specific targets to destroy mycobacterial cell assembly, and important botanicals which have shown anti-mycobacterial activities in research.