An ethno-medicinal investigation was conducted to highlights the traditional knowledge of medicinal plants being used by the tribe in West and South district of Tripura. This paper provides information about the different uses of plants used in their primary health care system. Tripura is a small north-eastern state of India and also a part of both Himalayan and Indo-Burma biodiversity region. It is a goldmine of medicinal plants and use of different plants in tribal traditional heath care systems has long history. Nineteen different tribes in Tripura, depend on natural resources at a great extent. This paper documented 113 medicinal plant species from 56 families along with their botanical name, local name, family name, habit, medicinal parts used, and traditional usage of application. The dominant families are Euphorbiaceae (7 species), Apocynaceae (6 species), Fabaceae and Rubiaceae (5 species each), Caesalpiniaceae, Asteraceae, Liliaceae and Verbenaceae (4 species each), Combretaceae, Labiatae, Malvaceae, Rutaceae and Zingiberaceae (3 species each). Tribes of Tripura have rich traditional knowledge on plant based medicine. Different parts of the plants in crude form/plant extracts/ decoctions/infusion or pastes are employed in diverse veterinary and human diseases by the tribe’s of Tripura in daily life.