Plants provide multiple ecosystem services that can, directly and indirectly, benefit the local community and beyond. This study assessed the diversity of the multiple uses of medicinal plants (MPs) and wild edible plants (WEPs) as well as associated local knowledge in Bako Tibe District, Ethiopia. Based on the recommendation of local authorities, eight key informants were selected out of the general informants (48) at eight sites. Ethnobotanical data were quantitatively analyzed through the use of use values, pairwise comparisons, and reference and direct matrix rankings. In total, 74 species from 61 genera and 36 families were found to have multiple uses. The Fabaceae family had the highest number of species (11), followed by the Moraceae family (eight). Trees were represented by 31 species. Twenty species were used to treat 22 human and livestock ailments. The highest preference ranking was recorded for Ocimum lamiifolium for treating febrile illness. Leaves (55.2%) and fruits (13 species) were the most commonly used parts for MP and WEP species, respectively. The highest use value was recorded for Cordia africana, among the top 10 multipurpose species. The findings showed that the most preferred MP and WEP species need further phytochemical and food nutritional analysis, respectively.