This chapter examines the gut-brain axis as a central determinant of neuroinflammation and neurological dysfunction, reframing the pathogenesis of diverse brain disorders as, at least in part, originating in gastrointestinal dysregulation. Contrary to the traditional view of the brain as an autonomous organ, current evidence highlights its integration within a neuroimmune and neuroendocrine network in which the gastrointestinal tract—and particularly the gut microbiota—functions as a pivotal regulatory hub of central nervous system (CNS) health. Microbial dysbiosis and loss of diversity compromise intestinal barrier integrity (“leaky gut”), permitting translocation of bacterial products such as lipopolysaccharide (LPS) into circulation. These endotoxins activate systemic immune responses and cytokine release, which, upon crossing the blood-brain barrier, stimulate microglial activation and propagate neuroinflammatory cascades. Such processes contribute to the pathophysiology of neurodegenerative (e.g., Alzheimer’s, Parkinson’s), neurodevelopmental (e.g., autism spectrum disorder), autoimmune (e.g., multiple sclerosis), and psychiatric (e.g., depression, anxiety, schizophrenia) conditions. Mechanistic pathways include bidirectional vagal signaling; microbiota-derived metabolites such as short-chain fatty acids, tryptophan catabolites, and bile acids; and gut-primed immune cells and cytokines that sustain CNS inflammation. Preclinical and clinical studies link microbial imbalance to hallmarks of neuropathology, including amyloid-β and tau deposition, dopaminergic neurodegeneration, aberrant synaptic pruning, and immune dysregulation, thereby implicating gut-derived mechanisms in disease initiation and progression. Therapeutic approaches targeting the gut-brain axis is also discussed, including probiotics and prebiotics to restore eubiosis, fecal microbiota transplantation (FMT) to reconstruct microbial ecosystems, dietary strategies enhancing neuroprotective metabolite production, and vagus nerve stimulation to engage the cholinergic anti-inflammatory pathway. Emerging precision medicine strategies integrating microbiome sequencing, personalized nutrition, synthetic biology, and artificial intelligence are highlighted as future directions in neuropsychiatric and neurodegenerative therapeutics. By bridging gastroenterology, neurology, immunology, and microbiome science, this chapter positions the gut-brain axis as a transformative paradigm for understanding and treating neurological disorders. It argues for a conceptual shift from a CNS-centric model to one that recognizes the gastrointestinal tract as both an initiating site and a therapeutic target in brain disease.