Neurodegenerative disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are intricate conditions with multiple contributing factors, including genetic, environmental, and increasingly acknowledged microbial elements. The human gut microbiome, a diverse assembly of microorganisms within the gastrointestinal tract, has become a crucial influencer of central nervous system (CNS) health via the gut-brain axis. This two-way communication system, which involves neural, immune, endocrine, and metabolic pathways, allows microbial signals to impact brain function, neuroinflammation, and the progression of diseases. Growing evidence from both animal and human studies suggests that imbalances in gut microbiota are linked to key characteristics of neurodegeneration, such as amyloid build-up, α-synuclein clumping, and microglial activation. This chapter explores recent research on the mechanistic understandings of how neurodegenerative pathology is influenced by metabolites produced by microbes, modulation of the immune system, and signaling through the vagus nerve. It also delves into the novel diagnostic and therapeutic potential of probiotics, dietary changes, and fecal microbiota transplantation. At the same time, it recognizes current challenges in reproducibility, standardization, and clinical application. By incorporating emerging multi-omics approaches and personalized medicine frameworks, the gut microbiome presents significant potential as a transformative frontier in managing and preventing neurodegenerative diseases.