A series of new vanadyl complexes of ligands, N′-[(2-pyridine-2-yl-methylene)2-(phenylamino)] acetohydrazide (HL1), N′-[(2-hydroxybenzyl-2-yl-methylene)2-(phenylamino)] acetohydrazide (HL2), 4-azocyanoacetamidoanlilne antipyrine (HL3), 4-azocyanoacetamido-m-toludine (HL4), 4-azomalononitrile antipyrine (HL5) and 4- formylazohydrazoaniline antipyrine (HL6) have been prepared and physio-chemically characterized by using variety of analytical, spectral, and magnetic measurements. The analytical and spectral data showed that the ligands HL1 and HL2 behave as neutral bidentate ligands, coordinating via the azomethine nitrogen atom and the hydrazo carbonyl group; whereas, HL3 forms binuclear VO(II) complex, the ligand linked to two VO(II) ions, one of ions coordinated to the pyrazolone carbonyl group and NH group and the second ion linked to the hydrazo carbonyl oxygen atom and azo (N=N) group. The rest of coordination number 5 is satisfied by bidentate sulfate group. The HL4 and HL5 behave as neutral bidentate ligands coordinating through the pyrazolone carbonyl group and NH group, in case of ligand HL5 in addition to the mentioned mode, (C=N) and (C≡N) group participated to bind a second VO(II) ion to form binuclear complex. HL6 behaves as a neutral bidentate ligand reacted in its enol form via the azomethine nitrogen atom and OH group. The magnetic and electronic spectral data showed that the VO(II) complexes exhibit a square pyramidal geometry. Results revealed that the oral administration of vanadium complexes significantly reduced the blood glucose level in diabetic rats. The normalization of altered biochemical parameters upon vanadium complexes treatment indicates the improved glucose homeostasis. The antidiabetic activity of vanadium complexes is structural-dependent where complexes 2, 4 and 6 exhibited potent antidiabetic activity while the other complexes have no antihyperglycemic activity. Further study is recommended to investigate the structural-activity relationship of vanadium complexes.