The use of medicinal plants by nutraceutical, cosmeceutical and pharmaceutical industries is gaining more attention around the globe. Dioscorea bulbifera L. (Family: Dioscoreaceae) commonly known as ‘air potato’ is an important edible medicinal plant use to treat a wide range of diseases. Its traditional usage is well-recognized in the Chinese medicinal systems as well as in West Africa. Previous studies have demonstrated that D. bulbifera is effective against several therapeutic diseases such as cancer, goiter, skin infections, pharyngitis and orchitis. However, kidney and liver damage by this species is also reported by several researchers. The increasing demand of D. bulbifera mostly the tuber (underground part), as well as illegal/unsustainable harvesting has brought this valuable species to the threatened category. Therefore, more extensive research including different in vitro biotechnological approaches is still required in order to guarantee its sustainable utilization and long-term conservation. In addition, toxicity, safety evaluation and extensive clinical trials are required to check its therapeutic potential. The present review summarizes the synthesis of the current advances of scientific information on the ethnomedicinal uses, pharmacology, toxicity and potential role of modern plant biotechnology tools for the conservation of this high value plant.