The protective ability of corrosion inhibitors for steel in aqueous saline solutions is ensured for the metal potentials and pH values transferring, according to the Pourbaix diagram, the Fe–H2O system into a thermodynamically stable state of hydrated oxides of Fe (III). Under these conditions, the binary mixtures of the inhibitors of oxidation and salt passivation form highly efficient synergistic compositions that may provide the full protection of the metal. For aqueous saline solutions, the isomolar series method is proposed and its expediency is proved for the purposeful design, investigation and optimization of the composition of inhibiting mixtures with synergistic effects. It is shown that the complex-forming process plays a predominant role in the protective mechanism of inhibiting mixtures based on organic ligands that are capable to form weakly soluble complexes with metal ions. On this bases of the proposed approach, we develop highly efficient inhibiting mixtures for the protection of steel in aqueous saline solutions.