Abstract: Recent studies have found that antidepressant drugs can inhibit the growth of various bacteria and fungi, disrupt biofilms, and synergize with antimicrobial agents to enhance bactericidal effects and reverse drug resistance, offering a potential new approach to combat drug-resistant pathogens. This paper reviews the antimicrobial effects and mechanisms of different classes of antidepressant drugs and discusses the challenges they may face in antimicrobial infection therapy, such as the lack of in vivo experiments and clinical evidence, unclear pharmacology and toxicology and undefined active components. Further research is needed to promote their clinical application.