Endodontic and periapical lesions are prevalent infectious diseases primarily caused by bacteria and their metabolic byproducts. The most widely used treatment method today is root canal therapy, which aims to remove infectious substances from the root canal. Root canal sealers can fill areas that core filling materials cannot reach, effectively reducing the risk of reinfection through their antimicrobial properties thus improving the success rate of root canal treatment. Various strategies have been employed to enhance the antimicrobial efficacy of root canal sealers through different mechanisms such as mechanical interlocking or chemical bonding. These strategies include antibiotic modification, quaternary ammonium compounds modification, nanoparticle modification, and others. Overall, antimicrobial modification strategies are increasingly diverse, and their effectiveness in enhancing the antimicrobial properties of sealers is beyond doubt. Root canal sealers modified with quaternary ammonium compounds and nanoparticles have shown certain advantages in antibiofilm activity and have potential clinical prospects. However, whether these modified materials have longterm antimicrobial effects, whether they can perform similarly in vivo as they do in vitro, and their biocompatibility are issues that still need to be addressed. In the future, the preparation of root canal sealers with ideal multidimensional properties will require further long-term and in-depth exploration.