Loose nanofiltration membrane exhibits significant advantages in removing organic pollutants due to its high selectivity at a lower operating pressure. Herein, a novel zwitterionic loose polyamide separation layer was designed and formed on the modified polyethersulfone substrate to obtain the zwitterionic loose nanofiltration (ZLNF) membrane with high water permeability and good antifouling properties. The BAPP-TMC polyamide layer was fabricated by the interfacial polymerization between 1,4-bis(3-aminopropyl)piperazine (BAPP) and trimesoyl chloride (TMC). Afterward, the BAPP-TMC polyamide layer was grafted with zwitterions by a facile surface modification. Owing to the fabrication of the relatively loose polyamide structure with zwitterions, the prepared ZLNF-0.2 membrane presented an ultra-high pure water permeability of 148.5 L m−2 h−1 bar−1 while maintaining relatively good removal capacities for organic pollutants. The removal rates for humic acid (HA, 100 ppm) and Congo Red (CR, 100 ppm) were 98.1 % and 97.6 %, respectively. Furthermore, the good hydrophilicity and strong surface hydration effect of zwitterions endowed the ZLNF membranes with excellent anti-organic fouling and antibacterial adhesion properties. The good antibacterial abilities of ZLNF membranes were also proved by the fluorescence staining results. Due to the effective separation performance and good antifouling properties, the fabricated ZLNF membranes present great application potential in removing natural organic matter and dyes.