Clays are naturally occurring ingredients of many natural health products, being included in most of ancient Mediterranean/European medical texts and currently used to prepare therapeutic hot-muds (peloids) in several thermal stations of the Mediterranean region. Clays are included in the formulation of peloids as vehicles of the mineral-medicinal water, to obtain inorganic gels with rheological and thermal properties suitable to be topically applied. Knowledge about formulations and preparation procedures of these traditional medicines has been orally transmitted since ancient times. Increasing recognition of the therapeutic utility of these traditional and natural health care substances make necessary a full ethnopharmaceutic research to ascertain those compositional characters that allow to establish quality attributes and corresponding requirements for these materials and products, including identity, purity, richness and safety.Five clay samples (A, B, C, D and E) currently used in various spa centers of southern European/Mediterranean countries were studied. X-Ray diffraction (XRD) and X-ray fluorescence (XRF) data were used to asses sample identity and richness. Elemental impurities and microbiological contaminants were also determined and compared to normative limits. Particle size distribution was related to their safety as powder materials.Samples A, C, D and E were identified as "high purity clay", while sample B was identified as a mix of clay minerals and carbonates. The presence of carbonates in this sample could compromise its suitability for pelotherapy. The studied clays meet the main normative limits for metals impurities, with the exception of arsenic in sample A and nickel in sample B. The samples comply with the microbiological limits proposed by European legislation for medicinal products. According to the particle size of the studied samples, prevention and control of dust exposure must be considered.Despite their demonstrated longevity, the use of clays in traditional medicine formulations as peloids greatly requires comprehension of their identity and safety attributes. Continuity of these mineral substances as recognized health care ingredients oblige to conduct interdisciplinary research to know the features that sustain their traditional use in the preparation of medicines (ethnopharmaceutics).