Nanofiltration (NF) is considered as a promising technology for the removal of trace organic compounds (TrOCs) for wastewater reclamation, while a simultaneous low rejection of salts is desirable for the ease of using the reclaimed water. This study was conducted to exploit the potential of polypiperazine-amide NF membranes in achieving selective separation of TrOCs and NaCl by varying the concentration of the diamine monomer, piperazine (PIP), for interfacial polymerization and by modifying the nascent membrane surface with hydrophilic monomers, diethanolamine (DEA) and monoethanolamine (MEA). Results showed that increasing PIP concentration could decrease the membrane pore size and reduce the surface negative charge density, which led to an increased rejection of xylose and a reduced rejection of NaCl. The grafting of DEA or MEA molecules could further decrease the NaCl rejection, substantially improve the water permeability and maintain an effective removal for eight pharmaceuticals (PhACs). The optimal membrane prepared with a PIP concentration of 2.0 wt % and subsequently modified by MEA exhibited a rejection of NaCl at 33.1% and an average rejection of PhACs at 90.8% in a 10 mmol/L NaCl solution under an applied pressure of 6 bar. The membrane could have an even higher selectivity when the NaCl concentration was increased to higher levels. These results demonstrated the feasibility and versatility of the membrane in separating TrOCs from NaCl for wastewater reclamation.