Objectives: Recent studies have demonstrated that periodontal ligament-derived (POL) cells have the potential to regenerate a complete periodontal connective tissue attachment apparatus on both root and artificial substrates. The major objecffve was to study the cytotoxic characteristics of dental materials conduCive to periodontal regeneration. An experimental model was established using markers 'Of mesenchymal origin (vimentin) and both fibroblastic (a-smooth muscle actin) and osteoblastic (alkaline phosphatase and osteocalcin activity) phenotype. Materials and methods: Cell viability and proliferation assay were used to evaluate cellular response in 24, 48 and 72 hours incubation period of treatment with the tested materials: one composite resin, one light-cured composite cement, one self-cured composite cement and one glassionomer cement. Results: Using Poisson regression analysis, it was found that within the first 24 hours only the light cured and the self cured composite cement revealed a statistically significant cytotoxic effect (p < 0.05). After 48 and 72 hours of treatment all materials proved to the prominent cytotoxic with the light cured composite cement to have the most dominant effect in all time intervals. ConClusions: All materials were found to be cytotoxic to human POL cells. However, both type of material and time, affected cell viability and proliferation.