<p>The selection of the grafting monomer plays a pivotal role in determining the flocculation performance of chitosan-based grafted copolymers. In this work, the flocculation behavior and mechanism of chitosan-based graft copolymers with different grafting monomers (i.e. carboxymethyl chitosan-grafted polyacrylamide (CMCP), carboxymethyl chitosan-graft-poly (acrylamide-dimethyl diallyl ammonium chloride) (CMCPD), and chitosan-graft-poly (acrylamide-dimethyl diallyl ammonium chloride) (CPD)) on the kaolinite (001) surface were investigated using molecular dynamics simulations, flocculation experiments and flocs size measurement. The interaction energy calculations revealed that the copolymers exhibited the following order: CPD (− 943.105&#xa0;kcal/mol) &gt; CMCPD (− 522.812&#xa0;kcal/mol) &gt; CMCP (− 340.026&#xa0;kcal/mol). The calculated solvent-accessible surface area (SASA) showed that amphoteric CMCPD exhibited complete extension and unrestricted diffusion in solution, surpassing the capabilities of both CMCP and CPD. The diffusion coefficients of CMCPD, CPD, and CMCP, were determined to be 5.17 × 10^–10 m²/s, 2.68 × 10^–10 m²/s and 4.25 × 10^–10 m²/s, respectively. It can be inferred that the bridging ability of the CMCPD flocculant in solution is directly proportional to its higher diffusion coefficient. However, excessive adsorption of CPD onto kaolinite resulted in a reduction in the bridging capacity of CPD. The simulation results were validated by conducting flocculation experiments, and it was observed that CMCPD, possessing the strongest bridging capability, exhibited a significantly higher settling rate (19.47&#xa0;m/h) compared to CPD (12.56&#xa0;m/h) and CMCP (9.81&#xa0;m/h). The analysis of flocs particle size further confirmed the superior bridging ability of CMCPD, as evidenced by its largest flocs particle size, thereby facilitating rapid settling. This study provides valuable insights for the design and development of chitosan-based flocculants.</p> Graphical abstract <p></p>