This paper reports an ethnobotanical study that focused on the traditional medicinal plants used by local communities to treat human diseases. Ethnobotanical study of medicinal plants was carried out from June 25 to September 5, 2015, in Berbere district of Oromia region, Ethiopia. The study focused on documentation of medicinal plants used to treat various human diseases in the study area. Ethnobotanical data were collected using semistructured interviews, group discussion, guided field walks, and observations with participants. Preference ranking, paired comparison, direct matrix ranking, and informant consensus factors (ICF) were used to analyze the importance of some plant species. A total of 70 medicinal plants, distributed in 56 genera and 46 families, were collected and identified. Plant family with the highest medicinal plants in the study area used for various diseases treatment was Euphorbiaceae (11.4%). The result of growth form analysis showed that shrubs constituted the highest proportion of medicinal plants (48.6%). Roots, 43 (44.8%), were the most frequently utilized plant parts for preparation of traditional herbal medicines. Crushing was a widely used mode of preparation of traditional remedies where oral administration (37.5%) was the dominant route. The highest informants consensus factor (ICF) values were linked to gonorrhea and syphilis disease (0.95); the lowest was linked with external parasites and wound (0.69). Local people in the study area possess traditional knowledge of medicinal plants to treat various human ailments; however, agricultural expansion and disinterest of young generation became the major threat to medicinal plants. It is, therefore, necessary to preserve this indigenous knowledge on traditional medicines by proper documentation, identification of plant species used, and herbal preparation. To save medicinal plants from further loss, involving local communities in cultivation of the most utilized medicinal plants is recommended.