Endodontic treatments are significantly improved by the efficacy of root canal sealers against microbial invasion. This systematic review and meta-analysis focus on comparing the antimicrobial efficacy of nanoparticle-modified bio-ceramic endodontic sealers with conventional bio-ceramic sealers. This review adhered to PRISMA guidelines and included both in vitro and ex vivo studies after a comprehensive search in PubMed, Embase, and Web of Science. The antimicrobial property of the bioceramic sealers was analyzed through the colony forming units (CFU), the diameter of inhibition zone and microbial viability. Eleven studies were used for the analysis. Overall, results from the meta-analysis indicated that modified bio-ceramic sealers exhibit an enhanced antibacterial effect compared to their conventional counterparts. A standardized mean difference was computed across 11 studies and 28 sub study groups, revealing a significant antimicrobial effect size in favor of the nanoparticle-modified bio-ceramic sealer. However, high heterogeneity among studies was observed. Chitosan, silver and bioactive glass were among the common nanoparticles used to modify bio-ceramic sealers. A 2% concentration of chitosan nanoparticles showed the highest antimicrobial effect size. Despite the heterogeneity found in the study, the findings suggest that the modification of bio-ceramic sealers with nanoparticles possesses the potential to advance endodontic treatments. The promising direction of these nanoparticle enhancements indicates a valuable progression in endodontics, advocating for additional research and development to optimize the use of nanoparticles in clinical settings. / Oral Biology