An ethnobotanical study was conducted from October 2005 to June 2006 to investigate the uses of medicinal plants by people in Zegie Peninsula, northwestern Ethiopia. Information was gathered from 200 people: 70 female and 130 males, using semistructured questionnaire. Of which, six were male local healers. The informants, except the healers, were selected randomly and no appointment was made prior to the visits. Informant consensus factor (ICF) for category of aliments and the fidelity level (FL) of the medicinal plants were determined. Sixty-seven medicinal plants used as a cure for 52 aliments were documented. They are distributed across 42 families and 64 genera. The most frequently utilized plant part was the underground part (root/rhizome/bulb) (42%). The largest number of remedies was used to treat gastrointestinal disorder and parasites infections (22.8%) followed by external injuries and parasites infections (22.1%). The administration routes are oral (51.4%), external (38.6%), nasal (7.9%), and ear (2.1%). The medicinal plants that were presumed to be effective in treating a certain category of disease, such as 'mich' and febrile diseases (0.80) had higher ICF values. This probably indicates a high incidence of these types of diseases in the region, possibly due to the poor socio-economic and sanitary conditions of this people. The medicinal plants that are widely used by the local people or used as a remedy for a specific aliment have higher FL values (Carissa spinarum, Clausena anisata, Acokanthera schimperi, Calpurnia aurea, Ficus thonningii, and Cyphostemma junceum) than those that are less popular or used to treat more than one type of aliments (Plumbago zeylanicum, Dorstenia barnimiana).