The synthesis of a new family of 1,3-di(1,3,4-oxadiazol-2-yl)benzene derivatives is reported. Their structures were characterized using standard spectroscopic techniques such FT-IR, ¹H-NMR, ¹³C-NMR spectroscopies and mass spectrometry. The antidiabetic potential of these synthetic molecules was evaluated by determining their in vitro inhibitory activity against pancreaticα-amylase enzymes. In addition, in silico molecular docking and pharmacokinetic simulations were performed to examine the compounds binding interactions with the enzyme active site and to assess their ADMET properties. Compared the used positive control, the obtained results show that all 1,3-di(1,3,4-oxadiazol-2-yl)benzene derivatives demonstrated a good potency to inhibit the α-amylase enzyme, Especially, the 2,2'-(1,3-phenylebis(1,3,4-oxadiazole-5,2-diyl))dianiline (5d) with IC50 of 0.393 mg/mL. Furthermore, the experimental findings were supported by molecular dynamics, docking and ADMET studies. The obtained data emphasizes compound 5d as potential as safe and effective therapeutic agents targeting the pancreatic α-amylase enzyme.