Tehran University of Medical Sciences Journal of Medical Bacteriology 2251-8649 14 1 2026 02 11 62 72 EN Elhidar Najoua Laboratory of Microbial Biotechnology, Agrosciences, and Environment (BioMAgE), Labeled Research Unit-CNRST N°4, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech Katif Chaimaa 1 Laboratory of Microbial Biotechnology, Agrosciences, and Environment (BioMAgE), Labeled Research Unit-CNRST N°4, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech 40000, Morocco. 2 Research Unity. Phycology, Blue Biodiversity & Biotechnology—P3B, Laboratory of Plant Biotechnology, Ecology and Ecosystem Valorization, Faculty of Sciences, Chouaïb Doukkali University, P.O. Box 20, El Jadida M-24000, Morocco. Ait Hammou Hanane 3 High Institute of Nursing Professions and Health Techniques, Marrakech 40000, Morocco. 4 Laboratory of Anthropogenetics, Biotechnologies and Health, Faculty of Sciences of El Jadida, Chouaïb Doukkali University, El Jadida 24000, Morocco. 2025 10 07 2025 11 08 Background:   Antimicrobial resistance (AMR) mediated by efflux pumps constitutes a critical health problem, necessitating urgent strategies for the development of new efflux pump inhibitors (EPIs). In this regard, artificial intelligence (AI) seems to be an innovative strategy for accelerating discovery, optimization, and understanding of EPIs mechanisms of action. Conclusion:   This review summarizes recent advances regarding the role of AI in the development of new EPI, with emphasis on machine learning (ML) based inhibitor prediction, molecular dynamics (MD) for binding analysis, and quantitative structure-activity relationship modeling (QSAR). By regrouping data from recent studies, we discuss here the important role played by AI in the improvement of lead identification, inhibitor designs, and the study of the resistance mechanisms. Despite current limitations such as limited, fragmented data and structural complexity of efflux pumps, AI offers great promise to revolutionize EPI development. In order to effectively combat AMR, we address here some key approaches, applications, challenges, and future directions, demonstrating the urgent need for interdisciplinary collaboration. https://jmb.tums.ac.ir/index.php/jmb/article/view/633