A series of eleven hydroxy and methoxy substituted new chalcone oximes (2a-2k) were synthesized by the condensation of chalcone (1a-1k) with hydroxylamine hydrochloride in pyridine. Structures of the synthesized compounds were characterized using NMR (1D; H-1, C-13/APT and 2D H-1-H-1 COSY, NOESY and ROESY), FT-IR, UV, LC-MS spectral data and elemental analysis. These synthetic compounds (2a-k) were screened for their a-glucosidase inhibition. The most a-glucosidase inhibitory activity were observe on compounds 2a and 2b with in the range of 1.61-3.36 mu M (IC50 values) which were more active then acarbose (IC50, 13,34 mu M). IC50 values of other synthesized compounds 2c-2h are within the range of 7,25-25,55 mu M which were more or as active as acarbose, but, IC50 values for compounds 2j-2k were not observed. The geometric isomers of compounds 2a-2k were calculated theoretically. Experimental and theoretical calculations showed that cisoid 1E,2E is the most stable geometrical isomer of all.