Objectives: The most important requirement for the materials to be used in medical applications is its biocompatibility. Dental composite materials come into close contact with oral tissues, especially with gingival cells. Due to this close and long-term contact, the materials should exhibit a high degree of biocompatibility. The aim of this doctoral thesis was to certify that the modern composite materials are biocompatible and safe for clinical use and also, was to evaluate their cytotoxic and/or genotoxic effect on human fibroblasts ex vivo and gingival cells in vivo. Materials and Methods: Ex vivo cytotoxicity and genotoxicity of two contemporary commercial composite materials (Kalore, Vertise flow) on human gingival and pulpal fibroblasts depending on the concentration of the used material (20 mg/ml, 40 mg/ml), were tested using the ethidium bromide/acridin orange viability staining and an alkaline single-cell gel electrophoresis technique (comet assay). Genotoxicity was also assessed in gingival epithelial cells in vivo. Class V composite restorations were placed in 30 adult patients using two different composite resins. Cell samples were collected by gentle brushing gingival area along the composite restoration prior to, 7 days, 30 days, and 180 days following the restoration of the tooth. DNA damage was analysed for each cell sample by comet and micronucleus assay. Results: Ex vivo tested dental composites revealed statistically significant increase in the tail length and tail intensity in treated human gingival and pulpal fibroblasts, independent of the applied concentration. Cultures treated with nano-hybrid composite material Kalore (20 mg/ml) have been showed more genotoxic than those treated with self-adhesive flowable composite Vertise flow. In vivo results showed significantly higher comet assay parameters (tail length and % DNA in the tail) within 30, and 180 days of treatment. While the micronucleus tests for the same exposure time showed a higher number of cells with micronuclei, karyolysis and nuclearbuds. Results did not reveal the difference between the two composite materials for the same exposure time. Conclusion: We can conclude based on the results that the use of composite resins causes cellular damage. However, taking into consideration the high efficiency of DNA repair mechanisms, the results should not be considered as an absolute indicator of genotoxicity potential. As dental composite resins remain in close contact with oral tissue over a long period of time, further research on their possible genotoxicity are desirable.