Clays and muds have been used for centuries as cosmetics or pharmaceutical products for various therapies. The suitability of muds and clays for health- and beauty-related applications depends on their physicochemical properties, mineralogical composition, particle characteristics and toxicity. In this work, the physicochemical characterization of 12 mud specimens from different natural spa resorts in Greece and one from Israel (Dead Sea) is presented. All specimens were sterilized at 121 °C for 20 min, because of their intended use. The Greek mud specimens were collected from various locations in Macedonia, Western Greece and Northeast Aegean. All muds were characterized concerning their mineralogical, chemical components as well as their morphological characteristics using appropriate methods [powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), nitrogen absorption specific surface area measurements (BET), scanning electron microscopy and energy dispersive X-ray spectroscopy]. The concentrations of F−, Cl−, NO3− and SO42− anions at equilibrium with the mud specimens were measured by ion chromatography. Total calcium concentration was measured using atomic absorption spectroscopy, and the concentration of total N, C, H and S in the solids was measured using elemental analysis. Moreover, total phenolic concentration (TPC) in distilled water equilibrated with the mud specimens was measured as an index for their antioxidant properties. Several muds were found to present high TPC. Several of the examined mud specimens were found to have the potential use as pharmaceuticals or cosmetics. Based on the physicochemical characteristics of the mud specimens examined, possible improvement in their use and applicability has been suggested.