Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are characterized by progressive neuronal loss, accompanied by cognitive and motor impairments. Despite significant research efforts, effective disease-modifying therapies remain elusive. Emerging evidence implicates gut microbiome dysbiosis, an imbalance in the composition and function of gut microorganisms, as a critical factor in the onset and progression of these disorders. Through the gut-brain axis, a bidirectional communication system involving neural, immune, endocrine, and metabolic pathways, gut microbes significantly influence central nervous system (CNS) function and integrity. Microbial metabolites such as short-chain fatty acids (SCFAs), lipopolysaccharides (LPS), and tryptophan-derived compounds have been shown to modulate neuroinflammation, microglial activity, blood-brain barrier permeability, and oxidative stress, thereby contributing to neurodegenerative mechanisms. This chapter explores how gut dysbiosis may act as a driving force rather than a secondary consequence of neurodegeneration. We critically review evidence from both animal models and human studies to identify disease-specific microbial patterns and mechanistic links. Furthermore, we examine how diet, antibiotic exposure, and lifestyle influence gut microbial balance and their implications for neurodegenerative risk. Finally, we evaluate emerging microbiome-targeted interventions, including probiotics, prebiotics, postbiotics, dietary modifications, fecal microbiota transplantation, and precision microbiome editing, highlighting their therapeutic potential and limitations. Integrating insights from microbiology, immunology, and neuroscience, this chapter underscores the central role of the gut microbiome in neurodegeneration and presents innovative avenues for prevention and treatment.