This study aimed to explore microbial community dynamics in neurodegenerative diseases through metagenomic analysis, focusing on how microbial diversity and composition vary among Control, Alzheimer’s Disease, Parkinson’s Disease, and Multiple Sclerosis groups. We conducted a cross sectional study with 400 participants, analyzing fecal samples via metagenomic sequencing. Our results revealed significant differences in microbial alpha and beta diversity across groups. The Control group exhibited higher alpha diversity compared to disease groups, particularly Alzheimer’s Disease, which had notably reduced alpha diversity. Beta diversity analysis using PCA and PERMANOVA highlighted distinct microbial community compositions between groups. Differential abundance analysis showed increased levels of Proteobacteria and Actinobacteria in disease states. Correlation with clinical parameters indicated that reduced alpha diversity correlated with older age and longer disease duration. These findings suggest that microbial dysbiosis is associated with neurodegenerative diseases and may provide insights into potential microbial biomarkers or therapeutic targets.