In this paper, we report a series of eighteen novel pyrimidine-based thiourea compounds with good to excellent yields (61-88%). The chemical structures of these heterocycles consist of a central pyrimidine ring with phenyl-substituted thiourea motifs. The enzyme inhibitory potential of these compounds was investigated against alpha-glucosidase as this enzyme plays a crucial role in treating type II diabetes mellitus. Compounds 4i (IC50 = 22.46 +/- 0.65 A mu M), 4f (IC50 = 25.88 +/- 0.40 A mu M), 4h (IC50 = 27.63 +/- 0.49 A mu M), 4c (IC50 = 29.47 +/- 0.42 A mu M), and 4e (IC50 = 32.01 +/- 0.42 A mu M) delivered better inhibition than the reference compound acarbose (IC50 38.22 +/- 0.12 A mu M). The quantitative structure-activity relationship of the synthesized compounds was also studied.