Ethnobotanical study of medicinal plants in selected kebeles of Jeldesa cluster, Dire Dawa Administration, eastern Ethiopia was carried out with the aim of assessing and documenting the indigenous knowledge of medicinal plants used in the communities and preserves it to be used by the next generations. Ethnobotanical data collection was carried out from September 2015 to March 2016. Three study sites (kebeles) were selected purposefully based on the preliminary survey and recommendations of elders in the study area. Ethno-botanical data were collected using semistructured interviews, field observations and group discussion. About 24 informants (21 male and 3 female) were involved in this study. A total of 52 medicinal plant species belonging to 43 genera and 30 families were documented for the management of 48 human ailments; with details on their local name, family, habit, habitat, and their mode of preparation and mode of administration. Fabaceae had a relatively high number of species 7(13.5%), followed by Lamiaceae 4 (7.7%). Shrubs constituted 23 species (44%) followed by herbs 19 species (37%). Oral route contributed (57.7%) of the total species, followed by dermal (27.1%). Most of these species (83%) were wild and harvested mainly for their leaves (34%). Most herbal remedies are prepared using fresh plant materials (48%) in the form of crushing (31%). Ailment categories with high ICF value were swollen body parts (Gofla), wounds, and poisonous animal bites that had ICF values of 0.68, 0.66 and 0.64, respectively. Fidelity level index of Euphorbia somalinsis, Xanthium spinosum and Tribulus terrestris for kidney problem, Crotalaria laburnifolia for constipation, Eulophia petersii for swollen body part/GOFLA and Barleria orbicularis, Solanum sepiculum and Echidnopsis dammanniana for snake poison showed a fidelity level of 100% this indicated their outstanding preference for treating the corresponding ailments. The results of the present study also showed that deforestation and human encroachment were ranked 1st and 2nd as threats to conservation of medicinal plants. The present paper represents significant ethnobotanical information on medical plants which provides baseline data for future pharmacological and phytochemical studies.