Molybdenum disulfide nanosheets (MoS₂) were dispersed in β-cyclodextrin (β-CD) aqueous solution and interfacially polymerized with toluene-2,4-diisocyanate (TDI) to prepare high flux polyurethane loose nanofiltration membrane (DSPU) with good hydrophilicity and highly negatively charged. Through infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and energy dispersive spectrometer (EDS), the existence and distribution of MoS₂ nanosheets in DSPU were characterized and confirmed. Based on the pure water flux, salt, and dye rejection rate, The optimal composition of β-CD and MoS₂ in the aqueous phase was investigated. The pure water flux of DSPU-1.2–0.006 reaches 78.44 L/m²•h•bar, which is 2.4 times higher than that of the DPU membrane without MoS₂ and can retention the molecular weight >416 g/mol highly negatively charged small dye molecules. The interception behavior of DSPU on 10 kinds of dye molecules with different charge abilities, molecular weight, and size was investigated. The chemical composition, cavity structure, and MoS₂ nanosheet spacing of β-CD were analyzed for their correlation with DSPU interface properties, functional layer structure, and separation performance. DSPU worked stably for a long time and had an excellent antifouling performance. It has potential application performance in the field of dye desalination, separation, and purification.