In this investigation, Mn-Al and Cu-Al as layered double hydroxide (LDH) adsorbents were prepared by co-precipitation method and Calcined/Cu-Al (Cu-Al LDO) was prepared by heating Cu-Al at 500 °C for sulfate (SO42−) removal from aqueous media. Results show that the Cu-Al LDO has the better adsorption capacity compared with Mn-Al and Cu-Al toward SO42−. To improve the selectivity and capacity of Cu-Al LDO, hybrid nanocomposites were obtained by in situ formation of an inorganic network (Cu-Al LDO) in the presence of organic compounds. Surfactants such as N-Alkyl-N,N-dimethyl-N-benzylammonium chloride (NDBA) and cetyltrimethylammonium bromide (CTAB) are employed as organic compounds. The samples were characterized by N2 isotherm, XRD, FTIR and SEM-EDX with mapping, followed by SO42− adsorption studies. Central composite design (CCD) under response surface methodology (RSM) was used for the optimization of variables for the SO42− uptake from waters using prepared samples. The interactive influence of four variable input parameters viz. initial concentration, adsorbent dose, time and pH were assessed. The adsorption mechanisms that controlled the SO42− adsorption were surveyed based on the adsorption thermodynamics and adsorption kinetics as well as adsorption isotherms. Furthermore, the effect of competitive anions and desorbing agents at different concentrations on the adsorption and desorption of SO42− was explored, respectively.