Background: This research aims to collect and preserve ethnopharmaceutical knowledge based on the customs of the Tolaki-Mekongga tribe in treating various diseases experienced by people in the Tolaki-Mekongga tribal area. Methods: In this study, descriptive-qualitative methods have been used for the research objectives to be achieved. Qualitative methods have been used to identify plants as traditional medicines by interview, while quantitative methods have been used for the classification of medicinal plants, use of therapeutic plant organs, medicinal plant use formulations, determination of a group of plants as candidates for herbal medicine, phytopharmaca candidates, and even endemic plant as drugs candidates for tropical and infectious diseases. Results: The results obtained 158 medicinal plant species, although most of these medicinal plants were used by other tribes, and the Tolaki-Mekongga tribe only uses as many as ten medicinal plant species as local wisdom in the region. According to the survey results, it was found that the parts of the plant that were commonly used were roots, root water, stems, leaves, flowers, seeds, fruits and rhizomes. The processing of plants used as medicinal plants generally still uses traditional methods. Based on the questionnaires and field surveys, several things were found: through questionnaire data, as many as 133 respondents obtained online and offline were identified 158 plant species used by the Tolaki-Mekongga tribe to treat 112 types of diseases. A literature search shows that among the 158 plant species, several plants are not only used by the Tolaki-Mekongga people but also by other tribes in Indonesia and the world, but this study provides essential information and found that ten medicinal plant species are only used by the species of Tolaki-Mekongga partly have not been identified, namely: (tawa nggateba/kateba: local name), Kleinhovia hospita L., (tawa tamaseu: local name), (bajakah: local name), (tawa tanggedaso: local name), chlorophyll trees (spesies unidentified), (saumompai: local name), (katolanondoke: local name), Discidia albifora, and Discidia major. Conclusion: Data on endemic plants in the Kolaka and East Kolaka districts were obtained, which were used as medicinal plants and even as foodstuffs in the region and have the potential for herbal and phytopharmaca studies, so that phytochemical and pharmacological studies were needed to identify bioactive compounds.