A new series of 2,4,6-triaryl pyrimidine derivatives were synthesized in order to investigate their α-glucosidase inhibitory activity in vitro. The designed pyrimidine derivatives 4a-k was synthesized in good yield (55-86%) via a two-step reaction. The structure of the synthesized compounds was confirmed by different spectroscopic techniques (IR, NMR, and Mass spectroscopy). The in vitro α-glucosidase inhibition activities of the synthesized compounds 4a–k was also evaluated against Saccharomyces cerevisiae α-glucosidase. All the synthesized compounds showed α-glucosidase inhibitory activities except compounds 4e, 4i and 4j. Compounds 4d and 4f were the most active with IC50 values of 168.9 ± 6.7 and 228.4 ± 8.4 μM respectively. The kinetic study also revealed that compound 4d was a competitive inhibitor with Ki of 166 μM. Molecular docking study was performed for the two most active compounds.