Increasing the roughness of polyamide surface is recognized as an effective way to enhance their water permeability, however, this method also increases the fouling risk of the membranes. In this study, we present a type of enhanced nanostructured nanofiltration (E-NF) membrane, which was created by the simple addition of sodium bicarbonate during interfacial polymerization on a porous substrate. Water flux of the enhanced nanostructure NF membrane (E-NF) was nearly triple that of the control NF membrane (C–NF), while salt rejection was maintained at a high level. More importantly, the E-NF exhibited less fouling than the C–NF and a stripe nanostructure NF membrane (S–NF). This improved fouling resistance was a result of the enhanced ridge-and-valley nanostructure, which experienced reduced fouling coverage, as evidenced by non-destructive optical coherence tomography (OCT). Our results demonstrate the importance of surface nano-morphologies for improving membrane performance and provide new insight into methods which can be used to enhance the anti-fouling ability of nanofiltration membranes in applications such as water and wastewater treatment.