The gut microbiota or gut flora encompasses diverse microorganisms, including bacteria, viruses, yeasts, archaea, and fungi that regulate gut health and overall body function. These microbes communicate with the body through neural, endocrine, and immunological pathways. Disruption in gut microbiota, known as gut dysbiosis, impairs these systems, contributing to neurodegenerative diseases, predominantly Alzheimer’s, Parkinson’s, and multiple sclerosis via the gut-brain axis. Gut dysbiosis compromises the intestinal barrier, increasing permeability and allowing bacterial metabolites and proinflammatory mediators to enter circulation, damaging the blood-brain barrier and triggering neuroinflammation. Probiotics such as Lactobacillus acidophius, Bifidobacterium longum, and Lactobacillus helveticus R0052 have demonstrated neuroprotective effects in several preclinical models of neurodegenerative diseases. However, their gastric degradation limits their effectiveness. Nanotechnology-based probiotics (nano probiotics), including nanofibers and nanoparticles, have emerged as an effective strategy by enhancing bioavailability, increasing oxidative resistance, site-specific delivery, and nerve regeneration, offering a promising therapeutic strategy for neurodegenerative disease management. This book chapter highlights the potential role of gut microbiota in neurodegenerative diseases and the neuroprotective effects of probiotics enhanced through nanotechnology.