BackgroundPlants have been used as a traditional medicine for many years for the people of Wolaita, Ethiopia. The aim of the study was to record these local knowledge of the peoples who inhabit the Diguna Fango district. MethodsA semi-structured interview was conducted with a total of 60 informants. ResultsTotally, 50 species belonging to 24 families were identified to treat 28 human and livestock ailments. Solanaceae (14.3%) was the most abundant family whereas; the rosaceae (1.00) had the highest family use value (FUV). Most of the plants (82%) were reportedly used to treat human diseases. Herbs (34%) were the dominant growth habits, followed by trees (33%). The leaves (30%) were identified as the most used plant part. The most common methods of remedy preparations were eating and chewing (18.2% each) followed by grinding (13.61%). Oral (73.3%) was the major route of administration, followed by dermal (21.7%). The cardiovascular system diseases category (1.00) had a higher informant consensus factor value followed by the fever disease category (0.90). Croton macrostachyus Hochst. ex Delile, Commelina benghalensis L., Triticum dicoccon (Schrank) Schübl and Pentas spp. (100%) had a higher fidelity level to treat swelling, chirt (skin diseases), weight gain, and bone fractures, respectively. Persea americana Mill. was ranked highest as the most preferable medicinal plant for various purposes by local people, followed by Acacia abyssinica Benth. The principal threatening factors reported were charcoal production (26%), agricultural expansion (15%), and firewood (14%). Out of the plants and their uses documented, 16% of the medicinal plants and 28.6% of the uses were novel. ConclusionsThe present study indicated the existence of indigenous knowledge of medicinal plants to treat human and livestock ailments. Therefore, there should be mentoring for the local people in the study area to conserve their indigenous knowledge and resources.