The release of antibiotics into the environment has increased remarkably due to the extensive use of these pharmaceuticals worldwide. Sulfamethoxazole (SMX) and trimethoprim (TMP), two antibiotics proposed in the 3rd Watch List (WL) under the Water Framework Directive (Directive 2000/60/EC) and often prescribed together, were selected as representative pollutants. This study investigates volcanic soil collected from Monte Vulture (PZ, Italy) as a material tested to remove SMX and TMP from wastewater. XRD showed that volcanic soil was composed of 33.95 % pyroxene, 34.41 % olivine, 21.25 % albite, and 10.39 % muscovite. Preliminary tests revealed that this material was an excellent adsorbent of TMP but not of SMX. The presence of metal like Fe and Al makes it capable of activating oxidizing agents such as potassium peroxymonosulfate (PMS). In fact, experiments showed that the SMX was efficiently degraded under the test conditions. Additionally, a systematic study was performed to evaluate the influence of the most critical factors, such as initial antibiotic concentrations, liquid-to-solid ratio, and reaction time on the removal efficiency. The range of levels evaluated for each factor was selected according to the level of information they can provide. A central composite design coupled with response surface methodology was used. From a statistical analysis of the results, the main effects and interactions between variables were estimated. A polynomial model was also developed and validated to provide a mathematical description of the removal process. Overall, the results of this study suggest that the proposed approach could represent a valuable strategy for in situ and ex situ remediation of antibiotic-contaminated waters and soils.