The isolation of the unsymmetrical Schiff bases posed some challenges. Majority of unsymmetrical Schiff bases reported in the literature were synthesized via a stepwise approach. There are only a few procedures which proceed via a one-pot condensation approach because the introduction of different carbonyl groups might lead to the formation of a mixture of products. But by fine-tuning some of the reaction conditions we were able to isolate the desired unsymmetrical Schiff bases at room temperature. The new synthetic procedure for the preparation of the unsymmetrical Schiff bases was developed in our laboratory. The isolation of the unsymmetrical Schiff bases and their VO(IV) complexes as well as some of the symmetrical Schiff bases and their complexes generated in this research work was considered to be novel. The in vitro and in vivo insulin-mimetic studies show that majority of the Schiff base complexes of VO(IV) were active and two of the complexes were as active or more active than insulin. The new results generated in this work significantly advance scientific knowledge and make a useful contribution in the area of insulin-mimetic studies.