The human gut microbiota containing trillions of bacteria, archaea, viruses, and fungi is crucial for host physiology by regulating immune function, metabolism, and neurocognitive processes. With progressive aging, there are spectacular changes in microbial composition and diversity with a decline in beneficial taxa like Bifidobacterium and Faecalibacterium and an increase of proinflammatory pathobionts, resulting in dysbiosis. These changes are responsible for compromised intestinal barrier function, systemic low-level inflammation “inflammaging,” and immunosenescence, thus hastening the onset of chronic disease like metabolic syndrome, type II diabetes, cardiovascular diseases, neurodegeneration, and cancer. Mechanistically, microbiota-directed metabolites like short-chain fatty acids (SCFAs) determine epigenetic regulation, mitochondrial function, nutrient sensing pathways and autophagy, all of which are central hallmarks of aging. By contrast, a diverse, SCFA-producing microbiome has been associated with healthier aging and longer longevity. Recent findings point toward the therapeutic potential of microbiota-directed interventions like dietary modulation, probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and drug-based modulators like metformin. However, challenges are still there with respect to interindividual variation, limited longitudinal data, and translatability gaps between animal and human models. This chapter integrates current understanding of the interplay between microbiota and aging, unmasks underlying mechanisms, and assesses emerging microbiome-based therapeutic approaches toward health span enhancement and delay of age determined decline.