In our study, medium conditions were optimized for percent chemical oxygen demand (COD) reduction and drug removal from diclofenac sodium (DFS) solutions. Response surface methodology/central composite design was used for optimization. A. Campestris/Amberlite Styrene–divinylbenzene (XAD-4) biocomposite material was used as adsorbent. Four independent parameters (pH, initial concentration, interaction time and adsorbent amount) were chosen to optimize both % COD reduc-tion and DFS removal. As a result of experiments, maximum 77% COD reduction and maximum 98% DFS removal were obtained at 4 pH, 225mg/L initial concentration, 36min and 0.69 adsorbent amount. Scanning electron microscope and Fourier transform infrared spectroscopy devices were used for characterization of adsorbent material. To identify the isotherm for the adsorption mechanism, the Langmuir, Freundlich, Temkin and Harkins–Jura isotherm equations were examined. The Freundlich isotherm had 96.2% regression coefficient (R2) and was linear, so had better fit compared to the other equations and the adsorption mechanism abided by the Freundlich isotherm. The results show that statistical optimization design was successfully applied to experiments and A. Campestris/Amberlite XAD-4 is an appropriate biocomposite adsorbent with specific affinity for % COD reduction and removal of DFS from aqueous solutions under optimal conditions.