Peoples have used traditional human and veterinary medicine to treat diseases for generations. An ethnobotanical study was conducted at Dale district in Sidama Region, Ethiopia. The objective of this study was to document indigenous medicinal plant utilization and the factors affecting it. A total of 90 informants 66 male and 24 females (including 20 key informants) were selected and snowball sampling techniques was used. Ethnobotanical data were collected using semi-structured interviews, field observations, guided field walk, group discussion, preference ranking and paired comparison with traditional medicine practitioners. The Ethnomedicinal uses of 55 plant species which are distributed across 52 genera and 36 families were documented used as cure for 38 ailments. Among these, 31 medicinal plants were reported for human ailments treatment, 7 for livestock and 15 for both human and livestock ailment treatment. The most frequently utilized plant parts were leaves. Intestinal parasite ailment was reported as common problems. Oral administration observed as dominant one. Preference ranking analysis indicates that Vernonia amygdalina ranked first and most effective medicinal plant to cure intestinal parasite problems in human. While for livestock ailment, Achyranthes aspera ranked first and most effective medicinal plant to cure pneumonia. In paired wise comparison Stephania abyssinica ranked first and most effective medicinal plant to cure jaundice in humans as compared to the others. Informant consensus analysis showed that ailments like rabies, poisoning and snake bite scored the highest value (0.98), while pneumonia and jaundice scored the lowest values (0.63) respectively. Agricultural expansion, fire wood, deforestation and cash crop expansions were reported as driving factors for loss of medicinal plants.