Purpose This study aimed to evaluate the cytotoxic effects of different types of contemporary GICs on human dental pulp cell (hDPCs) and mouse fibroblast (L929) cultures. Methods Three high-viscosity GICs (HVGIC; GC Equia Forte, Riva Self Cure, IonoStar Plus), three resin-modified GICs (RMGIC; Photac Fil, Riva Light Cure, Ionolux), and a metal-reinforced GIC (MRGIC; Riva Silver) were investigated. Twelve disc-shaped specimens of each material were prepared and stored in Dulbecco's modified Eagle medium (DMEM). L929 fibroblasts and DPCs were then cultured in 96-well plates. Uncultured DMEM was used as a negative control. Mitochondrial dehydrogenase activity (MTT) assays were performed to detect cell viability after 24, 48, and 72 h. Data were analysed using Mann-Whitney U and Friedman tests followed by a Bonferroni-corrected Wilcoxon signed rank test, with the statistical significance set at P < 0.05. Results Toxicity levels varied between the cell-culture systems. MTT assays of L929 cells showed significant differences in percentages of viable cells, as follows: Riva Self Cure = Riva Silver > GC Equia Forte > IonoStar Plus = Riva Light Cure = Photac Fil > Ionolux. MTT assays of DPCs showed the percentages of viable cells to be significantly lower for the Ionolux group when compared to the other GICs, which did not differ significantly from one another. With the exception of Ionolux, none of the other GICs tested showed any toxicity, and in fact, they all induced cell proliferation (> 100% cell viability). Conclusions Although the degree of toxicity varied between the two cell-culture systems investigated, all the GICs tested, with the exception of Ionolux, performed favorably with regard to cytotoxicity (> 100% cell viability in both cell systems).