Clay, or more precisely, certain clay typologies, have been used traditionally by humans for therapeutic, nutritional, and skin-care purposes though they may be responsible for some relatively rare but significant health and skin-care risks. For example, clay particles could adsorb and make available for elimination or excretion any potential toxic elements or toxins being ingested or produced, but they could also adsorb and make available for incorporation, through ingestion or through dermal absorption, toxic elements, e.g. heavy metals. Geophagy has been observed in all parts of the world since Antiquity, reflecting cultural practices, religious beliefs, and physiological needs, be they nutritional (dietary supplementation) or as a remedy for disease. Some clays and clay minerals are employed widely in both the pharmaceutical and cosmetics industries as active compounds/agents and as excipients. In the biomedical field, some clay minerals such as halloysite and montmorillonite are known for their effective role as carriers for the control and sustainable delivery of active drug molecules, and in the biomaterials field some clay minerals are used for scaffold, hydrogel, foam, and film production. Constraints, both chemical and microbiological, on the use of clay-based products for therapeutic and cosmetic topical applications are generally imposed by sanitary regulations, and some solutions are proposed herein to control and reduce such restrictions. Particular emphasis is placed here on peloids and pelotherapy, as well as on manipulated and modified peloids, and specifically on tailored peloids or ‘designed and engineered’ peloids, and their derivatives, bactericidal peloids and ointments. As far as the so-called ‘killer clays’ are concerned, their pre-requisites, mechanisms of action, and disinfection role are also enhanced. Podoconiosis is an environment-related or geochemical disease that occurs in tropical highland areas, and is caused by long-term exposure of bare feet to volcanic, red-clay soil and affects some people, particularly those working in agriculture in some regions of Africa, Asia, and South America.