We report for the first time on the effect of biocompatible hexagonal boron nitride (h-BN) nanopowder reinforcement with different concentrations on the structural and mechanical properties of fabricated self-cured polymethyl methacrylate (PMMA) based dental materials (GC UNIFAST III). A comparison among the structural and mechanical properties between hand and ultrasonic mixing is also presented. Fabricated specimens were studied by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectrometry (FTIR), micro indentation, and flexural strength techniques. The ultrasonic mixing method provides better sample textures of the composite as compared to hand mixing. It is found that XRD and IR intensity of the peaks increases with the increase of h-BN concentration due to nanocomposite formation. The additions of h-BN nanoparticles to the acrylic resin enhanced the hardness and the flexibility values of the composites. Independently of the mixing method used, adding h-BN nanopowder relatively increases the Vickers Hardness numbers (VH) and Flexural Strength (FS) of the unmodified materials. However, using ultrasonic mixing method combined with h-BN nanopowder increases VH numbers to 300% and FS values to 550% with respect to the unmodified sample made by hand mixing. The results obtained are very encouraging and will support future research in vivo, to confirm whether PMMA loaded with h-BN nanoparticles is an improvement compared to current dental restorative materials.