The main purpose of this research work is to characterize zinc oxide-urea formaldehyde nano resin and identify the physical performance of medium-density fiberboard (MDF). Considering the dry weight of natural fibers, the ZnO nanoparticles were added to urea formaldehyde (UF) glue at four levels—0.0%, 1.0%, 2.0% and 3.0%—and their effects were investigated in terms of the physical properties of MDF. The surface morphology and crystalline structure of ZnO, UF and UF-ZnO nanofillers were characterized using Scanning Electron Microscopy (SEM) and X-ray diffraction (XRD) analysis and significant improvements were achieved as a result of the addition of nanoparticles. Thermal properties were analyzed by means of differential scanning calorimetry (DSC) and thermogravemetric analysis (TGA) and it was observed that increasing the concentration of ZnO nanoparticles ultimately enhanced the curing of UF-ZnO nanofillers. Finally, density, thickness swelling and water absorption properties were investigated and it was observed that thickness swelling and water absorption properties were improved by 38% and 12%, respectively, when compared to control MDF.