This systematic review was designed to answer the following question: Does chitosan provide better smear layer removal and antimicrobial efficacy than other root canal irrigants? A literature search was done using electronic databases PubMed, Scopus, Web of Science, Cochrane Library, EBSCO host, Grey Literature Report, and Open Grey from inception to June 18, 2024. The reference lists of included articles were also hand-searched. Two reviewers independently assessed the studies' eligibility based on the inclusion and exclusion criteria and performed data extraction. Two reviewers independently evaluated the risk of bias in the selected studies. The search retrieved 2330 studies. After analysis, 36 studies fulfilled the eligibility criteria and were included, with 19 involving smear layer removal, 16 involving antibacterial efficacy, and 1 involving both. The overall risk of bias of the included studies was medium. Chitosan removed the smear layer more effectively than citric acid and acetic acid, similar to MTAD and Qmix, with conflicting results against EDTA. In addition, chitosan demonstrated comparable antibacterial efficacy to chlorhexidine, propolis, and photodynamic therapy but was less effective than sodium hypochlorite. Based on available evidence, it was found that chitosan provided better smear layer removal and antimicrobial efficacy than most root canal irrigants compared in this systematic review. There was substantial heterogeneity in the methodology of included studies. As a result, this review highly recommends further research using standardized methods to assess the effectiveness of chitosan as a root canal irrigant in in-vitro studies to validate its clinical use., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)