The gut microbiota plays a crucial role in regulating metabolic, endocrine, and immune functions, and recent studies have highlighted its involvement in modulating neurochemical pathways through the gut-brain axis. Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are key metabolites produced by bacterial fermentation of dietary fibers and resistant starch in the colon. These SCFAs are speculated to play a significant role in neuro-immunoendocrine regulation, influencing brain physiology and behavior. The review outlines the current understanding of how SCFAs contribute to microbiota-gut-brain interactions and their potential therapeutic applications in treating central nervous system (CNS) disorders. SCFAs can influence gut-brain communication through direct and indirect pathways, including the vagus nerve, immune system, hypothalamic-pituitary-adrenal axis, and tryptophan metabolism. They also affect brain function by modulating neurotransmitter levels, neurotrophic factors, and neuroinflammation. Additionally, SCFAs have been linked to various brain disorders such as autism spectrum disorder, mood disorders, Alzheimer's disease, Parkinson's disease, and multiple sclerosis, suggesting their potential as therapeutic targets. The review emphasizes the need for further research to fully understand the mechanisms by which SCFAs influence brain health and the development of treatments for CNS disorders.The gut microbiota plays a crucial role in regulating metabolic, endocrine, and immune functions, and recent studies have highlighted its involvement in modulating neurochemical pathways through the gut-brain axis. Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are key metabolites produced by bacterial fermentation of dietary fibers and resistant starch in the colon. These SCFAs are speculated to play a significant role in neuro-immunoendocrine regulation, influencing brain physiology and behavior. The review outlines the current understanding of how SCFAs contribute to microbiota-gut-brain interactions and their potential therapeutic applications in treating central nervous system (CNS) disorders. SCFAs can influence gut-brain communication through direct and indirect pathways, including the vagus nerve, immune system, hypothalamic-pituitary-adrenal axis, and tryptophan metabolism. They also affect brain function by modulating neurotransmitter levels, neurotrophic factors, and neuroinflammation. Additionally, SCFAs have been linked to various brain disorders such as autism spectrum disorder, mood disorders, Alzheimer's disease, Parkinson's disease, and multiple sclerosis, suggesting their potential as therapeutic targets. The review emphasizes the need for further research to fully understand the mechanisms by which SCFAs influence brain health and the development of treatments for CNS disorders.