Advanced glycation end products (AGEs) are formed in non-enzymatic reaction, oxidation, rearrangement and cross-linking between the active carbonyl groups of reducing sugars and the free amines of amino acids. The Maillard reaction is related to sensory characteristics in thermal processed food, while AGEs are formed in food matrix in this process. AGEs are a key link between carbonyl stress and neurodegenerative disease. AGEs can interact with receptors for AGEs (RAGE), causing oxidative stress, inflammation response and signal pathways activation related to neurodegenerative diseases. Neurodegenerative diseases are closely related to gut microbiota imbalance and intestinal inflammation. Polyphenols with multiple hydroxyl groups showed a powerful ability to scavenge ROS and capture α-dicarbonyl species, which led to the formation of mono- and di- adducts, thereby inhibiting AGEs formation. Neurodegenerative diseases can be effectively prevented by inhibiting AGEs production, and interaction with RAGEs, or regulating the microbiota-gut-brain axis. These strategies include polyphenols multifunctional effects on AGEs inhibition, RAGE-ligand interactions blocking, and regulating the abundance and diversity of gut microbiota, and intestinal inflammation alleviation to delay or prevent neurodegenerative diseases progress. It is a wise and promising strategy to supplement dietary polyphenols for preventing neurodegenerative diseases via AGEs-RAGE axis and microbiota-gut-brain axis regulation.