An ethnobotanical survey was carried out to collect information on the use of medicinal plants by the Zay people who live on islands as well as shore areas of Lake Ziway in the Ethiopian Rift Valley. A total of 33 medicinal plants were reported as being used locally for the treatment and/or control of human and livestock ailments. Results of the survey showed that leaf materials form the major component of plant parts harvested. The majority of the remedies are prepared in the form of juice from freshly collected plant parts. Most of the remedies are prepared from a single species, and are mainly taken orally. Most of the medicinal plants are collected from the wild. Of the total claimed medicinal plants, 10 were reported scarce locally. Environmental degradation and intense deforestation have been reported as the main causes for the depletion of medicinal plants in the area. As the Zay people are still partly dependent on medicinal plants, loss of these plants will, to a certain extent, hamper the existing health care system in the area. Measures for conservation of medicinal plants of the Zay people are urgently needed.