Background: Plants have a long history of being used for medicinal purposes, and a large proportion of people in the developing world still rely on traditional medicines to meet their primary health care requirements. Medicinal plants are the major components of the traditional health care system. The objective of this study was to record and document the medicinal plants and associated indigenous plant use knowledge of the local people in Kelala District of Amhara Region, Ethiopia.Methods: Ethnobotanical data were collected by conducting pre-prepared semi-structured interview items with 60 informants. Focus group discussion and guided field walk were also used. Data were analyzed using basic analytical tools and descriptive statistics. Determination of Informant Consensus Factor, Fidelity level, and ranking was performed. Results: A total of 82 medicinal plants distributed in 79 genera and 45 families were collected. Of these plants, 43 species were used to treat human ailments, and 33 species were used to treat livestock ailments and the remaining 6 species were used to treat both human and livestock ailments. The majority of medicinal plants were harvested from the wild environments. The family Solanaceae occupied the first rank with seven species followed by Fabaceae, Asteraceae, Cucurbitaceae, Apiaceae, and Euphorbiaceae with four species each. The most frequently used plant parts were leaves (42.2 %) followed by seeds (15.2 %), roots (8.1 %), and fruits (7.6%). Freshly harvested plant parts (72.68 %) were mostly used for remedy preparation than dried forms (24.74 %) whereas crushing, which accounted for (41.12%), and powdering (24.37%) were the most widely used methods of remedy preparation in the study area. Conclusion: Higher number of medicinal plants recorded in the study area indicates the depth of medicinal plant resources and associated indigenous knowledge of the local people. However, the expansion of farmlands by cutting trees heavily threatens medicinal plants and therefore, needs due attention. High ranking medicinal plants are good candidates for further research in drug discovery and development.