With rapid advances in synthetic biology and genetic engineering, genetically engineered bacteria (GEB) have emerged as a promising platform for biological therapy, addressing key limitations of conventional drug delivery systems and demonstrating significant clinical potential. By leveraging a modular design framework, GEB exhibits high biocompatibility and programmability, enabling precise genetic modifications for targeted delivery, dynamic responsiveness, and sustained therapeutic effects. This review systematically examines the therapeutic development of GEB, focusing on its pivotal roles in tumor therapy, inflammatory bowel disease (IBD), metabolic disorders, and the treatment of complex infections. It outlines key design strategies—including sensing, payload release, and biocontainment modules—as well as evaluation frameworks and mechanisms of action. We also discuss major challenges to clinical translation, such as the limited availability of clinically validated chassis strains, the balance between bacterial fitness and therapeutic load, and persistent biosafety concerns. Future progress will depend on advancements in high-precision genome editing, intelligent responsive systems, and interdisciplinary collaboration to bridge the gap between preclinical promise and clinical application. This review aims to provide an up-to-date reference to facilitate the translation of GEB from laboratory discoveries to viable clinical applications in precision medicine.
