<p><b>Aim</b> Antimicrobial resistance is an emerging global health challenge, driven largely by the overuse of antimicrobial drugs. However, the extent of mouthwash-induced antimicrobial resistance remains poorly understood. This systematic review aimed to assess the influence of commonly used mouthwashes on antimicrobial resistance, focusing on resistance genes, microbial alterations, and cross-resistance to antibiotics.</p><p><b>Methods</b> PubMed, Scopus, Web of Science, and grey literature, including Google Scholar, were searched for studies evaluating mouthwash-induced antimicrobial resistance. The search strategy included terms related to ‘oral microbiome', ‘mouthwash' and ‘antimicrobial resistance', with Boolean operators tailored to each database. Risk of bias was assessed using <i>In Vitro</i> Critical Appraisal Tool for <i>in vitro</i> studies and the Modified Joanna Briggs Institute for <i>ex vivo</i> and <i>in vivo</i> studies, respectively.</p><p><b>Results</b> Twelve studies were analysed, comprising seven <i>in vitro,</i> four <i>ex vivo</i> and one <i>in vivo</i> study. A total of 91 patients and 213 bacterial isolates were assessed across various mouthwashes, including chlorhexidine digluconate, cetylpyridinium chloride, hydrogen peroxide and others. Due to heterogeneous outcomes, a meta-analysis was not conducted. The findings consistently revealed increased minimum inhibitory concentrations of oral bacteria and the presence of resistance genes, highlighting a potential rise in antimicrobial resistance.</p><p><b>Conclusion</b> This systematic review indicates a possible association between mouthwash use and resistance-related changes in the oral microbiome; however, the limited and heterogeneous evidence base warrants cautious interpretation. Further, longitudinal research is needed to elucidate the underlying mechanisms and inform evidence-based guidelines for mouthwash use.</p>