Background: The main objective of endodontic therapy is to adequately clean and seal the root canal system. According to Grossman et al, idealistically root canal sealers must be dimensionally stable, produce a tight seal after setting and exhibit an adequate setting time. They should also be insoluble and provide adequate adhesion with the root canal walls. Therefore, the present study was conducted to evaluate some physio-chemical characteristics of novel poly-dimethyl-siloxane gutta-percha calcium-silicate containing sealer (GuttaFlow bioseal) in contrast with a commercially available zinc oxide and eugenol sealer (ZnO/E). Materials and Methods: Flow, setting time, working time, film thickness and dimensional changes were evaluated for Guttaflow bioseal and contrasted to a commercially available zinc oxide and eugenol sealer (ZnO/E) following the ADA specification number 57. Results: In Flow, setting time and working time tests; ZnO/E sealer showed higher mean values than that of GuttaFlow bioseal with an extremely significant difference, while film thickness of GuttaFlow bioseal was significantly higher than that of ZnO/E sealer. Results of dimensional changes test showed a significant difference between both sealers, where GuttaFlow bioseal exhibited a positive mean value, while ZnO/E exhibited a negative mean value. Conclusions: It can be concluded that; GuttaFlow bioseal might be an acceptable substitute to zinc oxide and eugenol sealer. New researches in-vivo and in-vitro should be postulated for better interpretation of the physical properties of endodontic sealers.