In this work, Mg-Al layer double hydroxide (Mg-Al LDH) nanoparticles were synthesized through co-precipitation technique. Then, a novel polyvinylidene fluoride (PVDF) mixed-matrix ultrafiltration (UF) membrane containing the synthesized Mg-Al LDH nanoparticles was fabricated via the phase inversion technique. The nanoparticle and membrane were characterized by Fourier transform infrared spectroscopy (FT-IR), Field emission scanning electron microscopy (FESEM), X-Ray diffraction (XRD), Water contact angle (WCA), and Atomic force microscopy (AFM). The effects of polymer, pore-former, and nanofiller contents were studied to find the optimum membrane by the stepwise procedure. The obtained results showed that with increasing the content of Mg-Al LDH nanoparticles up to an optimum value (0.5 wt%), surface hydrophilicity, average pore size, porosity, roughness, and antifouling properties of the fabricated mixed-matrix membranes considerably improve. The pure water flux, BSA rejection, and the flux recovery ratio of 213 L/m(2) h, 98.8%, and 94.8%, were achieved, respectively. Finally, the simulation of concentration, velocity, and pressure profiles on the optimum membrane was performed, which covered the experimental results with 0.2% discrepancy.