Diabetes mellitus is a chronic endocrine disorder that affects the metabolism of carbohydrates, proteins, fat, electrolytes and water. α-Amylase and α-glucosidase are the crucial enzymes required for the digestion of the carbohydrate. These enzymes play a vital role in the breakdown of starch in the diet and its activity has been correlated to postprandial blood glucose levels, the control of which is essential for maintaining the quality of life for diabetic patients. We report the synthesis, characterization and biological evaluation of new substituted 2-phenoxynicotinaldehydes as α-amylase inhibitors. A new general method based on the aromatic nucleophilic substitution reactions of 2-chloronicotinaldehyde with differently substituted phenols in the presence of K2CO3 in dry dioxane was developed to furnish the corresponding substituted 2-phenoxynicontinaldehydes with 70-80% yields.