This study deals with the mineralogical and thermal analysis of red clay taken from the south of Tunisia (Tataouine area) which will be used in industrial and environmental fields. In that purpose the study had recourse to several quantitative and qualitative research instruments: chemical analysis, mineralogical study and thermal analysis. The analyses were carried out by different methods such as: (i) X-ray diffraction (XRD), (ii) infrared spectroscopy (IR), (iii) thermogravimetric analysis (TGA), (iv) differential thermal analysis (DTA) and (v) cation exchange capacity (CEC). The data collected from these techniques show that illite and kaolinite are the major clay phases. The accessory minerals detected in powdered rock is calcite. The raw clay has undergone an acid activation using the sulfuric acid. The acid activation of south of Tunisia clay increase the specific surface area by adsorption of methylene blue from 117 m2/g to 163 m2/g. The experimental investigation is performed in accordance with the methodology of the factorial design of experiments. The different factors or parameters used in this methodology are: the temperature (T), the contact time (t), the liquid/solid ratio (R), and the acid concentration (C). The optimal conditions, obtained by the statistically designed experiments, for the best results of methylene blue adsorption were: 60 °C, a contact time of 1.5 h, a liquid/solid ratio of 7 and acid concentration of 20%. These parameters are applied in the preparation of the sample used in characterization study. The effect of the reaction conditions on the solid structure is investigated by comparison with the raw clay sample.