Background:The success of the endodontic treatment is largely dependent on the sealing achieved by root canal obturation. The application of sealer fills imperfections and increases adaptation of the root filling to the canal walls. Aim:To evaluate the sealability of experimental nanosealers (nano calcium hydroxide and nano bioactive glass) and to compare it with the commercial zinc oxide eugenol sealer using a dye penetration method. Materials and Methods:Sixty single-rooted mandibular premolars were selected. The tooth crowns were removed so as to obtain standardized 15-mm-long root specimens. The root canal was instrumented with Protaper Ni-Ti rotary file and the final file size was up to # F4/.06 (in vitro study). They were then randomly allocated into 3 groups of 20 specimens each (n=20) according to the sealer used for obturation, and all samples were filled with single cone guttapercha (#40/06) and one of the tested sealers. All teeth were coated with nail polish and then suspended in 2% methylene blue dye for 7 days. Stereo-microscope (x10) was used to evaluate the sealability of newly introduced nanosealers. The data were statistically analyzed by ANOVA test followed by post hoc analysis (P < 0.05). Results:Significant improvement shown by the presented study suggests that nano calcium hydroxide sealer showed significantly less dye leakage than nano bioactive glass sealer and zinc oxide eugenol sealer. Conclusion:The results of this study showed that the synthesized nano-powder sealers are suitable for use in root canal therapy to prevent leakage.The root canal can be sealed better by using smaller nano-powder particle sizes. In addition, the two groups exhibited significant differences in leakage in comparison with commonly used ZOE sealer.