<p>The gut microbiota plays a crucial role in maintaining host metabolic balance and immune homeostasis, with increasing evidence linking its dysregulation to neurodegenerative diseases and cancer. This review aims to provide a comprehensive and integrative analysis of gut microbiota-mediated immune modulation in Parkinson’s disease, Alzheimer’s disease, and cancer. A structured literature-based approach was employed to examine recent studies focusing on microbial composition, metabolite production, and host microbe immune interactions. We summarize the role of key microbial metabolites, particularly short-chain fatty acids, in regulating immune responses, maintaining gut barrier integrity, and modulating systemic inflammation. In addition, the bidirectional communication along the gut–brain axis is discussed, highlighting its differential involvement in neurodegenerative disorders, while microbiota driven immune mechanisms contributing to tumorigenesis are also evaluated. Importantly, this review emphasizes the translational relevance of microbiome-targeted interventions, including prebiotics, probiotics, synbiotics, and emerging postbiotic strategies, in modulating disease progression and therapeutic outcomes. Although limitations lies in correlating the human gut microbiota to the results obtained from the animal studies which may not fully reflect the physiological conditions of the human gut as it is affected by several factors, this work provides a unified framework linking gut microbiota, immune regulation, and disease pathogenesis, and outlines future directions for the development of targeted and personalized microbiome-based therapies which may be achieved through well designed longitudinal and large scale clinical studies further.</p>