BackgroundIn Ethiopia, medicinal plants have continued to play vital role in fulfilling human and livestock healthcare needs of different communities. However, these valuable resources are being depleted mainly due to agricultural expansion and deforestation. Therefore, immediate action is required to conserve these resources and document the associated knowledge. The purpose of this study was, thus, to document and analyze information associated with medicinal plants that are used in managing public and animal health problems in Seharti Samre District, Southern Tigray, Ethiopia.MethodsEthnobotanical data were collected from July 1, 2011 to December 30, 201 mainly using semi-structured interviews with informants sampled using purposive sampling technique and through field observations.ResultsThe study revealed the use of 90 medicinal plant species in Seharti Samre District for the treatment of several human and livestock diseases. The plants belonged to 46 families and 82 genera. The majority of the medicinal plants were indicated to be harvested from the wild. Leaf was the most frequently harvested plant part accounting for 44% of the reported plants, followed by roots (16%), whole plants (10%) and seeds (8%). The most widely used method of preparation was crushing (37%), pounding (15%) and chewing (13%). Most medicinal plants were applied internally (64.6%), followed by external application on the skin (35.4%). Febrile illness is the disease group in the study area that scored the highest ICF value (0.97), followed by cardio-vascular problems (0.97) and evil eye (0.95). Different preference ranking exercises were also used to determine the most preferred and potential medicinal plants in the study area.ConclusionIn Seharti Samre District, medicinal plants are still playing important role in the management of various human and livestock diseases, many of which are harvested for their leaf parts. However, activities of claimed medicinal plants need to be evaluated before recommending them for their wider use. Evaluation priority should be given to medicinal plants with the highest informant agreement as such plants are believed to have better activity.