Resin cement integrated with zein-incorporated magnesium oxide nanoparticles has previously been found to inhibit oral microbes and decrease bacterial biofilm. However, the bond strength and surface features of this biomaterial have yet to be investigated. The objective of this study was to evaluate the shear bond strength, mode of fracture, and surface roughness of resin cement modified with zein-incorporated magnesium oxide nanoparticles. Characterization of the cement was performed by X-ray diffraction, field emission scanning electron microscopy, and Fourier transform infrared spectroscopy. 126 human teeth were divided into 3 groups and cemented to lithium disilicate ceramic using resin cement with zein-incorporated magnesium oxide nanoparticles at concentrations of 0%, 1%, and 2% (n = 42). 21 samples of each group were subjected to the shear bond strength test, while the other 21 underwent thermocycling for 10,000 cycles before the test, after which all samples were evaluated for the mode of fracture. To assess surface roughness, resin cement disks were analyzed by a profilometer before and after undergoing thermocycling for 10,000 cycles. The shear bond strength of the cement with 1% and 2% nanoparticles was significantly higher than the control before thermocycling. The mode of fracture was found to be mainly adhesive with all groups, with the unmodified cement presenting the highest cohesive failure. There was no significant difference in surface roughness between the groups before or after thermocycling. The addition of zein-incorporated magnesium oxide nanoparticles to resin cement improved or maintained the shear bond strength and surface roughness of the resin cement.