The residue of microplastic in secondary effluent was inevitable with continuous aggravation on nanofiltration membrane fouling. Thus, this study aimed to further evaluate the applicability of electro-coagulation as pretreatment for improving the performance of a nanofiltration-oriented hybrid process during the reclamation of microplastic-contaminated secondary effluent. The electro-coagulation parameters were skillfully optimized and designed for following dynamic nanofiltration experiments. The potential influence of coagulants in different forms as well as their combined effects of microplastics on membrane fouling behaviors and pollutant rejection efficiency was distinguished. Specifically, terminal membrane permeability was reduced by 19% after 0.05 A electro-coagulation, while 0.2 A electro-coagulation almost eliminated the negative effects of microplastics. Mass transfer model analysis excluded the dominance of organic accumulation in the concentration polarization layer on membrane fouling development. Molecular dynamic (MD) simulation and egg-box model demonstrated that humic-Fe network possessed stronger bridging effects and greater porosity. This structure favored the co-deposition of other unlinked bacteria metabolites, which secretion was also facilitated by microplastics as immobilized carriers, on membrane surface. Additionally, density functional theory (DFT) calculation further confirmed that the greater demand for dehydration energy for ferric ions (1124 kcal/mol) inspired the formation of stronger humic-Fe complexes. Besides, residual microplastics in electro-coagulation effluent had different impacts on membrane rejection towards organic and inorganic pollutants, and it depended on the influenced cake-enhanced concentration polarization (CECP) by microplastic affinity with different pollutants.