Spa centres in northern Italy use clayey admixtures for the formulation of muds to be used in pelotherapy. The basic ingredient (“virgin” clay) is a dressed bentonitic geomaterial with mineralogical composition: smectite 60–70%, illite 5–10%, kaolinite 10–15%, quartz 5–10%, calcite 5–10% and feldspars 2–3%.The peloid muds are obtained by “maturation” of the virgin clay with mineral waters gushing out in situ which have different geochemistry: sulphureous, Ca-sulphate, Ca–Mg-sulphate and Br–I-salty (after the Italian regulation DPR 105/92). The maturation treatment is varying with respect to the mixing procedure and lasting time.Peculiar parameters have been tested to verify the effects of various maturation treatments, i.e., changes with respect to virgin clay.Formation of organic matter is due to the presence of microorganisms and algae in the maturation habitat. The <2 μm fraction is generally decreased due to clay particles agglomeration. Mineralogical changes are mainly concerning the degradation of clay minerals, as smectite and illite, and subordinately to the dissolution of calcite. Cation exchange capacity (CEC), soluble salts, water retention, swelling index, activity, consistency parameters (WL, WP and PI), thermal behaviour and cooling kinetics are influenced by the geochemistry of mineral waters used for the maturation treatments but with some opposite trends for Br–I-salty water, and for sulphureous and Ca-sulphate waters, respectively.Noteworthy was the influence of high-pH value of the virgin clay on the pH of peloid muds (in fact, the pH of the used mineral waters is ranging around the natural value). Furthermore, the temperature reached by the peloid muds after 20 min of application (calculated after an innovative mathematical model) is influenced by water retention. An increase in plasticity index and a slower cooling are considered to improve the quality of the obtained peloid muds for pelotherapy.The observed different cation exchange behaviour and soluble salt content could be discriminant for either dermatological masks or thermal body cataplasms.A need of regulation (standard procedures) is suggested to certificate the clay geomaterials suitable for pelotherapy and also for drugs formulation.