Ethnobotany is the study of interaction between people and plants. Much of Ethiopia's population, primarily receives their medical treatment from the usage of traditional herbal medicines. But across the country, human activity has been the primary cause of the degradation of natural resources. The study aims to document the indigenous knowledge about medicinal plants and to evaluate the antibacterial activities of some plants in the Telemt District. The ethnobotanical data was collected through semi-structured interviews, focus group discussions, field observations , and a market survey. Ethnobotanical data was analyzed using descriptive statistics, informant consensus factor, fidelity level, preference ranking, and direct matrix ranking. A total of 198 informants (143 general informants selected randomly and 55 key informants selected purposively) were selected from 8 study kebeles. A total of 113 medicinal plant species belonging to 57 genera and 59 families were documented, with 77 species used for human ailments, 16 for livestock, and 20 for both. Most medicinal plants were found from a wild environment. Fabaceae had the highest number of traditional medicinal plants with eight species (7.08%). Shrub constitutes the largest number of medicinal plants with 46 species . The most frequently used plant parts were leaves, accounting for 75.23%. Herbal remedies are prepared mostly using fresh plant material (64.4%). Crushing was the major method of preparation accounts (35.6%), followed by grinding accounts (20.42%). The major route of administration was oral accounting for 109 (57.07%) of preparation. The major way of application was drinking (40.43%). Agricultural expansion was a major threat to medicinal plants. Environmental protection was the major activity used by local communities. Significant differences were observed in the antibacterial activity of three selected medicinal plants (Brucea antidysenterica, Verbascum sinaiticum, and Withania somnifera). The antibacterial activities of these plants were evaluated against four bacterial strains using the agar well diffusion method. Among the three plants, the leaf extract of B. antidysenterica exhibited the highest antibacterial activity against Klebsiella pneumoniae, measuring 21 ± 0.471 mm.