Soils contamination with Cd result in detriment to the environmental quality. In-situ immobilization methods by applying clay minerals have been gaining prominence. The effects on sepiolite of thermal activation at different temperatures (300–750 °C), for removing Cd from aqueous solutions were evaluated, in order to consider their further application for soil remediation. The influence of activation temperature was investigated using XRD, SEM, and N2 adsorption-desorption measurements. The S-600 exhibited the maximum adsorption capacity (21.28 mg/g), despite its lower SSA, and Langmuir model described the adsorption isotherms better than the Freundlich equation. TCLP was used to quantify the remediation effects of thermal-activated sepiolite on simulated soils artificially polluted with Cd. The results indicated that the mobility of Cd in soil was effectively reduced after treating with thermal-activated sepiolite and the use of S-600 was the most efficient, reducing the TCLP-Cd by approximately 73% compared with the control test. The main remediation mechanism was considered as the cation exchange of Cd by Mg at the edges of octahedral sheet. This study showed that thermal-activated sepiolite could be promising amendments for remediation of Cd-contaminated soil.