Oxidovanadium(IV) complexes with 5-cyanopyridine-2-carboxylic acid (HpicCN), 3,5-difluoropyridine-2-carboxylic acid (HpicFF), 3-hydroxypyridine-2-carboxylic acid (H2hypic), and pyrazine-2-carboxylic acid (Hprz) have been synthesized and characterized in the solid state and aqueous solution through elemental analysis, IR and EPR spectroscopy, potentiometric titrations, and DFT simulations. The crystal structures of the complexes (OC-6-23)-[VO(picCN)2(H2O)]·2H2O (1·2H2O), (OC-6-24)-[VO(picCN)2(H2O)]·4H2O (2·4H2O), (OC-6-24)-Na[VO(Hhypic)3]·H2O (4), and two enantiomers of (OC-6-24)-[VO(prz)2(H2O)] (Λ-5 and Δ-5) have been determined also by X-ray crystallography. 1 presents the first crystallographic evidence for the formation of a OC-6-23 isomer for bis(picolinato) V(IV)O complexes, whereas 2, 4, and 5 possess the more common OC-6-24 arrangement. The strength order of the ligands is H2hypic ≫ HpicCN > Hprz > HpicFF, and this results in a different behavior at pH 7.40. In organic and aqueous solution the three isomers OC-6-23, OC-6-24, and OC-6-42 are formed, and this is confirmed by DFT simulations. In all the systems with apo-transferrin (VO)2(apo-hTf) is the main species in solution, with the hydrolytic V(IV)O species becoming more important with lowering the strength of the ligand. In the systems with albumin, (VO)(x)HSA (x = 5, 6) coexists with VOL2(HSA) and VOL(HSA)(H2O) when L = picCN, prz, with [VO(Hhypic)(hypic)](-), [VO(hypic)2](2-), and [(VO)4(μ-hypic)4(H2O)4] when H2hypic is studied, and with the hydrolytic V(IV)O species when HpicFF is examined. Finally, the consequence of the hydrolysis on the binding of V(IV)O(2+) to the blood proteins, the possible uptake of V species by the cells, and the possible relationship with the insulin-enhancing activity are discussed.