To shed light on the role of V(V) complexes as pro-drugs for their V(IV) analogues, the kinetics of the reduction reactions of [VO2(ma)2]- or [VO2(ema)2]- (Hma = maltol, Hema = ethylmaltol), with ascorbic acid or glutathione, have been studied in aqueous solution by spectrophotometric and magnetic resonance methods. EPR and 51V NMR studies suggested that the vanadium(V) in each complex was reduced to vanadium(IV) during the reactions. All the reactions studied showed first-order kinetics when the concentration of ascorbic acid or glutathione was in large excess and the observed first-order rate constants have a linear relationship with the concentrations of reductant (ascorbic acid or glutathione). Potentiometric results revealed that the most important species in the neutral pH range is [VO2(L)2]- for the V(V) system where L is either ma- or ema-. An acid dependence mechanism was proposed from kinetic studies with varying pH and varying maltol concentration. The good fits of the second order rate constant versus pH or the total concentration of maltol, and the good agreement of the constants obtained between fittings, strongly supported the mechanism. Under the same conditions, the reaction rate of [VO2(ma)2]- with glutathione is about 2000 times slower than that of [VO2(ma)2]- with ascorbic acid, but an acid dependence mechanism can also be used to explain the results for the reduction with glutathione. Replacing the methyl group in maltol with an ethyl group has little influence on the reduction rate with ascorbic acid, and the kinetics are the same no matter whether [VO2(ma)2]- or [VO2(ema)2]- is reduced.