Defluoridation of water using an economic method is important to combat the issue of excessive fluoride content (>1.5 mg/L), which is very detrimental to human health, in drinking water. In the present work, micelle templated mesoporous material, MCM-41, was synthesized and explored as an adsorbent for adsorption of fluoride ions from aqueous media and the process of adsorption was optimized through three levels of Box–Behnken design (BBD) of response surface methodology (RSM). The data obtained were found to be best fitted for Langmuir adsorption isotherm suggesting monolayer adsorption of fluoride ions on the surface of micelle templated MCM-41; Langmuir maximum adsorption capacity was found to be 52.91 mg/g. Optimization through BBD involves approximation of selected input of independent variables, i.e., initial fluoride concentration, solution pH and adsorbent dose with percentage removal of fluoride as the response variable. The quadratic model was suggested to predict the percentage removal of fluoride ions. As per the prediction, maximum removal of 82% can be achieved at initial concentration up to 21 ppm in pH range of 5.4–5.8 and adsorbent dose of 1–1.3 g/L. Experimental and model predicted values of adsorption were found to be in good agreement with each other.