Organic-inorganic hybrid nanocomposites are promising materials for remediation of pollutants from wastewater, as they exhibit the unique characteristics of both inorganic and organic materials. In this study, carboxymethyl cellulose/montmorillonite Nanocomposite (CMC/MMT-NC) was prepared and applied for Cu2+ sequestration. CMC/MMT-NC was characterized by FTIR and SEM before and after the sequestration process, indicating fundamental changes in surface morphology after treatment experiments. The parameters affecting the process such as pH, contact time, CMC/MMT-NC mass, Cu2+ concentration and temperature were experimentally adjusted. Statistical regression variables (R2, RMSE, RSS, F-Value and P-Value) were calculated to predict the best-applied isotherm, kinetic and thermodynamic modeling. Freundlich isotherm model successfully described the equilibrium data, which implies a multilayer adsorption process. Kinetic results were well fitted to pseudo-second-order kinetic model. Intraparticle diffusion (IPD) model showed the control of the boundary layer moreover, IPD model cannot be accepted as the only rate-determining step. The apparent activation energy (Ea) was 35.65 kJ/mol, which revealed a physisorption process. The thermodynamic study in means of ΔG0, ΔH0, and ΔS0 demonstrated the feasibility, spontaneity and exothermicity of Cu2+ sequestration. Application study confirmed the efficiency of CMC/MMT nanocomposite to remediate Cu2+ from synthetic and natural polluted seawater.