An ethnomedicinal survey on the traditional knowledge of tribes and other non-tribal communities of Kuldiha Wild Life Sanctuary of Balasore district of Odisha was undertaken by visiting 14 tribal-rich villages located in and around the sanctuary. The study was focused on ethnomedicinal plants used to treat various common diseases by the tribal communities reside in the study area. This communication deals with traditional use of 81 plant species belonging to 78 genera and 43 families along with correct botanical identification, local names, mode of administration in respect to different ailments. Crushing of plant or plant part(s) and extraction of juice was the widely used mode of preparation of remedies where oral administration was the principal route. Ethnomedicinal data were collected through semi-structured interviews with the native herbal practitioners and elderly knowledgeable persons using standard questionnaire and group discussion. Local inhabitants in the study were found to possess vast knowledge on medicinal plants to treat various human ailments. The use of these traditional medicines was observed to be widespread and prevalent over the modern medicines in the area. However, deforestation and lack of interest of young generation became the major threat to medicinal plants diversity in the area under study. It is, therefore, suggested to preserve this indigenous knowledge on ethnomedicines by proper documentation, identification of plant species and herbal preparation. The results of the present investigation further emphasize to take appropriate conservation measures to facilitate sustainable utilization of these plant resources.