Hoodia gordonii is a spiny succulent plant commonly consumed for its claimed anti-obesity effects. Traditionally, the Khoi-San people of South Africa and Namibia used it to suppress hunger and thirst during extended hunting expeditions. However, the commercialization of this plant has been highly contentious, largely due to disputes over intellectual property rights and benefit-sharing, as well as the withdrawal of interest from several major pharmaceutical companies involved in its development. Scientific studies have focused heavily on quality control, given the limited availability of H. gordonii due to its restricted geographical distribution, slow growth rate, the need for permits to cultivate or export it, and high public demand, which has led to widespread product adulteration. Although many steroidal glycosides have been identified in H. gordonii, the primary emphasis has been on P57, a pregnane glycoside thought to be the active component and a marker for determining the quality of raw materials and products. Despite this, there is a lack of scientific publications addressing key issues such as in vivo biopharmaceutics, the biological activity of all its chemical components, clinical effectiveness, and, most importantly, safety. This raises significant concerns, as H. gordonii is among the most widely consumed natural products for weight loss. This review offers an up-to-date-overview of all the current available knowledge pertaining to H. gordonii achieved by systematic analysis of the available literature.