BACKGROUND: Fluorosis is an endemic disease due to an excess of fluoride intake via drinking water. In some regions of the world, removing fluoride from drinking water is a severe problem that is still to be solved. The present study focuses on the use of a natural clay to reduce fluoride concentration in Tunisian contaminated drinking water under relevant working conditions. RESULTS: Adsorption experiments were performed in batches using a fluoride aqueous solution. The Box-Behnken model design was used to define the working conditions in which three factors were controlled: clay dosage, contact time and agitation speed. The fixed parameters were the initial fluoride concentration and water pH as observed in Metlaoui, Tunisia in 2021, and experiments were performed at room temperature. Results show that 4 g(50 mL) −1 of clay dosage, 10 min of contact time and 280 rpm of agitation speed could provide 51% fluoride removal using an untreated natural clay. Then, various adsorbents based on this clay were synthesized (chitosan-clay, C 6 H 17 NO 3 Si-clay and thermally treated clays purified using different methods) and tested using the same approach. Among the adsorbents tested, the thermally treated purified clays were the most effective in removing fluoride under ambient conditions with a fluoride removal of 97.5%. Tests performed on drinking water showed that the safety fluoride concentration could be achieved without modifications of the water pH. CONCLUSIONS:The thermally treated clays investigated in this study were effective for fluoride removal under relevant conditions, which can pave the way for future field applications.