Flavonoids and their precursor trans-chalcone have been reported as inhibitors of mammalian alpha-amylase. With regard to this background, neohesperidin dihydrochalcone (NHDC) effect was investigated toward porcine pancreatic alpha-amylase (PPA), and found to be an activator of the enzyme. The maximal activation (up to threefold) was found to occur at 4.8mM of NHDC, which could be considered to have a high activation profile, with regard to the alpha and beta parameters (alpha<1<beta). NHDC is a non-essential activator of the enzyme and based on the results obtained from modeling tools, it is suggested to interact with PPA at a hydrophilic site located at the N-terminal, far from the active site of the enzyme.