The indigenous people of different localities in the country have developed their specific knowledge on the use, management and conservation of plant resources.This Ethnobotanical study was conducted to asses and documents the use of medicinal plants by people of Simada District, South Gondar, Ethiopia. A total of 160 respondents were selected. Out of these, 24 key informants (16 males and 8 females) were purposively selected based on recommendation from elders and local authorities and the rest 136 were selected randomly. Data were collected using semi-structured interviews, field observations and group discussions.The data were analysed by using descriptive statistics, informant consensus, preference ranking, direct matrix ranking and fidelity level. A total of 98 plant species: 56 species from wild vegetation, 27 species from homegarden and 15 species from both wild and homegardens distributed in 81 genera and 45 families were collected and identified. From these, 58 species were recorded for the treatment of human health problems, 13 species for livestock and 27 species for the treatment of both human and livestock ailments. From the total medicinal plants species 44 species were herbs, followed by 37 species were shrubs,14 species of trees and 3 species were climbers.The most frequently used plant parts were leaves (42.7%) followed by roots (17.43%). The most widely used method of preparation was crushing (34.4%) followed by powdering (15.6%) followed squzeeing (13.8%). The common route of administration recorded was oral (56%) followed by dermal (29.81%), nasal and oral (5.5 %) and nasal (4.6%). The medicinal plants that is most effective in treating certain diseases such as Allium sativum, Carsia spinarum and Lepidum sativum have high informant consensus. Preference ranking showed that people of the area have preference for Rumex abyssinicus for the treatment of dihrrea. Direct matrix ranking showed that Cordia africana as the most multipurpose species by the community. Agricultural expansion, firewood, overgrazing and construction are major threats to medicinal plants in the study area.Encouraging the local people, give awareness and training on coservation and management of plants in general and medicinal plants in particular, in their community are recommended. Key words: Ethnobotsany, Homegardens, Indgenous knowledge, Medicinal plants, Simada