Indigenous knowledge is passed from generation to generation, usually by word of mouth and cultural rituals, and has been the basis for agriculture, food preparation and conservation, health care, education, and the wide range of other activities that sustain a society and its environment in many parts of the world for many centuries. Tuberand root crops are the third important group of food cropsafter cereals and pulses, feeding about one fifth of the world population. However, the study onindigenous knowledge of the community on underutilized and neglected root and tuber crops has not been so far investigated. Therefore, indigenous knowledge of the community on underutilized and neglected root and tuber crops was conducted in 120 randomly selected households at 10 different Kebeles (neighborhoods, the smallest administrative units in Ethiopia) within six potential growing districts of Sidama and Gedio Zones, SNNPR, Ethiopia. The result of this research confirmed that underutilized and neglected root and tuber crops used as traditional medicine in the study areas. According to the reports of the respondents the overall uses of underutilized and neglected root and tuber crops were for food, income sources, feed and traditional medicine. Almost all of the respondents use the underutilized and neglected root and tuber crops for food in the study area. Majority of the respondents (74%) were used the underutilized and neglected root and tuber crops for traditional medicinal use. Moreover, some of the respondents in the study reported that the underutilized and neglected root and tuber crops used as income source, food flavoring and for feed. Underutilized root and tuber crops and their wild relatives such as Ipomoea batatas, Colocasia esculenta, Dioscorea villosa, and Manihot esculenta have high bioprospecting potential for pharmaceuticals, bio-ethanol and food industries. Therefore, commercializing and bioprospecting those medicinal and food plant, would not only increase the Ethiopia’s economic growth, but also contribute to the global stock of pharmaceuticals, food and bio-fuel industries.