Objective: The objective of this study was to compare the potential mutagenicity of resin-, silicone-, and bioceramic-based sealers on proteinexpression in human lymphocytes. There has been limited research on resin-, silicone-, and bioceramic-based sealers effects on protein expressionin lymphocytes.Methods: Nine samples of each sealer were incubated in 2 mL human blood for 1, 3, and 7 days. Then, the isolated lymphocytes are observed forprotein separation by electrophoresis method. Profile of protein bands observed and data were analyzed statistically by Kruskal–Wallis and post hocMann–Whitney.Results: Although no statistically significant differences in protein bands were observed among the resin-, silicone-, and bioceramic-based sealers(p=0.111), there was a statistically significant difference between the resin- and silicone-based sealers on the 1st day (p=0.046) and 3rd day (p=0.046)and between the silicone- and bioceramic-based sealers on the 1st day (p=0.046). Thus, the present study shows that there were differences in thepotential mutagenicity on the 1st day; resin was potentially more mutagenic followed by bioceramic and silicone. On the 3rd and 7th days, bioceramicwas potentially more mutagenic followed by resin and silicone.Conclusion: The manuscript describes the study in detail and concludes that resin was potentially more mutagenic followed by bioceramic- andsilicone-based sealers.