Background:The potential of graphene-based materials to improve the physiomechanical properties of Portland cement-based materials without compromising biocompatibility is of interest to dental researchers and remains to be discovered.Aim:This study investigated the effects of adding graphene oxide nanoplatelets (GONPs) on the surface microhardness and biocompatibility of Portland cement.Materials and Methods:Three prototype Portland cement powder formulations were prepared by adding 0, 1, and 3 wt % GONPs in powder form to Portland cement. Prototype cement specimens were in the form of disks, with a diameter of 10 mm and a thickness of 2 mm. In experiment 1, surface microhardness was measured using the through indenter viewing hardness tester, 20 surface hardness values were obtained from all specimens. In experiment 2, Balb/C 3T3 fibroblasts were cultured with the material disks and the viability of cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Statistical Analysis:The data were analyzed using the analysis of variance followed by Dunnett test (α = 0.05) or Tukey test (α = 0.05).Results:In response to material disks, the addition of 1 wt % GONPs had a proliferative effect on cells at day 3 and day 7 with a significant difference from the control. The addition of 3 wt % GONPs showed a remarkable increase in surface microhardness; however, it exhibited initial cytotoxicity.Conclusions:The addition of 1 wt % GONPs to Portland cement improved surface microhardness without compromising biocompatibility; therefore, it has a greater potential for dental applications. The results of this work give other researchers leads in future assessments of this prototype material.