<p>The escalating crisis of antibiotic resistance presents a formidable challenge to global public health and food security. Insects are increasingly recognized as significant reservoirs and vectors for antibiotic resistance genes (ARGs) which inhabit diverse ecosystems. This review explores how the insect gut microbiota contributes to the development and spread of antibiotic resistance, focusing on the mediating role of the host immune system. We outline the structural and functional dynamics of the insect gut microbiome and elaborate on direct mechanisms through which microbiota contribute to resistance, including ARG carriage, enzymatic inactivation of antibiotics, and modulation of host detoxification pathways. Special emphasis is placed on the bidirectional crosstalk between gut microbes and the host immune system: we discuss how immune effectors, particularly antimicrobial peptides (AMPs), exert selective pressures that may enrich resistant taxa, and how microbial metabolites reciprocally regulate immune activity. Key immune signaling pathways—Toll, Immune Deficiency(Imd), and Janus kinase-signal transducer and activator of transcription (JAK-STAT)—are explored for their roles in maintaining microbial homeostasis and modulating resistance phenotypes. We also highlight cutting-edge experimental approaches, including gnotobiotic models and multi-omics technologies, that are essential for elucidating causal relationships. We conclude by highlighting outstanding questions and outlining future research priorities that integrate microbiology, immunology, and computational biology. This review aims to establish a holistic framework for understanding the insect gut as a hotspot for antibiotic resistance evolution and to inspire innovative microbiome-based interventions.</p>