The non-enzymatic interaction of sugar and protein resulting in the formation of advanced glycation end products responsible for cell signaling alterations ultimately lead to the human chronic disorders such as diabetes mellitus, cardiovascular diseases, cancer, etc. Studies suggest that AGEs upon interaction with receptors for advanced glycation end products (RAGE) result in the production of pro-inflammatory molecules and free radicals that exert altered gene expression effect. Till date many studies unveiled the potent role of synthetic and natural agents in inhibiting the glycation reaction at lesser or greater extent. This review focuses on the hazards of glycation reaction and its inhibition by natural antioxidants including polyphenols.