Graphene oxide (GO) loose nanofiltration (LNF) membranes show immense potential for the desalination of small organic molecules. However, it remains a significant challenge to compare the performance of GO LNF membranes prepared via different doping methods and study the mechanisms that influence the separation abilities of the membranes. In this study, LNF membranes prepared via three GO doping methods were examined for flux, retention rate, and the separation performance of small organic molecules and inorganic salts. The membranes coated with dopamine (DA) and GO, and subsequently formed polydopamine (PDA)–GO intercalation, showed the best results. A novel LNF membrane material (PVDF/PDA–GO–TFN; PVDF: polyvinylidene fluoride, TFN: thin-film nanocomposite) was developed to enhance the separation performance of small organic molecules and inorganic salts while improving membrane surface stabilization and anti-fouling performance and reducing the “trade-off” effect. The optimal conditions for PDA–GO intercalation and the best combination for interfacial polymerization (IP) were also determined. The intercalation structure was identified via scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy, atomic force microscopy, and Fourier-transform infrared spectroscopy. Furthermore, the separation mechanism of the membrane was determined to be based on the Donnan and steric hindrance effects, according to the correlation analysis of the membrane surface electrical properties (zeta potential), hydrophilicity (contact angle), and pore properties. The PVDF/PDA–GO–TFN LNF membrane displayed a maximum water permeance of 10.45 L/(m2·h·bar), with an 88 % rejection of PEG2000 and a 6.83 % rejection of Na2SO4. Moreover, the membrane exhibited excellent anti-fouling performance and long-term stability, with a mean flux recovery rate of 99.06 % after four cycles of filtration and backwashing tests using small organic molecules and inorganic salt solutions. The inorganic salt retention rate was analyzed using SPSS software, and the results indicated excellent membrane stability. In summary, the preparation of PVDF/PDA–GO–TFN membrane materials provides a novel approach for fabricating LNF membranes that can effectively separate small organic molecules and inorganic salts.