The increased consumption of a variety of herbs/supplements has been raising serious health concerns. Owing to an inadequate understanding of herb/supplement–drug interactions, the simultaneous consumption of these products may result in deleterious effects and, in extreme cases, even fatal outcomes. This systematic review is aimed at understanding the knowledge and beliefs about the consumption of herbs/supplements and herb/drug–supplement interactions (HDIs). The study follows the PRISMA guidelines. Four online databases (Web of Science; PubMed; Cochrane; and EBSCOhost) were searched, and a total of 44 studies were included, encompassing 16,929 participants. Herb and supplement consumption is explained mostly by the reported benefits across multiple conditions and ease of use. Regarding HDIs, most people take both herbs/supplements and prescription drugs simultaneously. Only a small percentage of participants have knowledge about their interaction effects, and many reported adverse interactions or side effects. Nevertheless, the main reason for stopping the prescribed drug intake is the perceived lack of its effect, and not due to interactions. Therefore, it is important to increase the knowledge about supplement use so that further strategies can be elaborated to better detect or be alert for whenever a potentially dangerous reaction and/or interaction may occur. This paper raises awareness regarding the need for developing a decision support system and ends with some considerations about the development of a technological solution capable of detecting HDIs and, thereby, aiding in the improvement of pharmacy services.