Drimia (synonym Urginea) plants are bulbous plants belonging to the family Asparagaceae (formerly the family Hyacinthaceae) and are distinctive, powerful medicinal plants. Just some species are indigenous to South Africa and have been traditionally utilized for centuries to cure various diseases and/or ailments. They have been recognized among the most famous and used medicinal plants in South Africa. Traditionally, the plants are used for various illnesses such as dropsy, respiratory disease, bone and joint complications, skin disorders, epilepsy and cancer. A number of studies have reported biological properties such as antiviral, antibacterial, antioxidant and anti-inflammatory, immunomodulatory, and anticancer activities. Their bulbs are a popular treatment for colds, measles, pneumonia, coughs, fever and headaches. However, some plant species are regarded as one of the six most common poisonous plants in Southern Africa that are toxic to livestock and humans. Due to the therapeutic effects of the Drimia plant bulb, research has focused on the phytochemicals of Drimia species. The principal constituents isolated from this genus are cardiac glycosides. In addition, phenolic compounds, phytosterols and other phytochemical constituents were identified. This study constitutes a critical review of Drimia species’ bioactive compounds, toxicology, biological properties and phytochemistry, advocating it as an important source for effective therapeutic medicine. For this purpose, various scientific electronic databases such as ScienceDirect, Scopus, Google Scholar, PubMed and Web of Science were researched and reviewed to conduct this study. Despite well-studied biological investigations, there is limited research on the toxic properties and the toxic compounds of certain Drimia species. Searching from 2017 to 2021, Google Scholar search tools retrieved 462 publications; however, only 3 investigated the toxicity and safety aspects of Drimia. The aim was to identify the current scientific research gap on Drimia species, hence highlighting a thin line between poisonous and healing compounds, dotted across numerous publications, in this review paper.