The superposition-additive approach developed and tested previously on monofunctional nonionic amphiphiles is updated and used for the calculation of the thermodynamic clusterization parameters for amphiphiles with two functional groups. In the framework of this approach the thermodynamic parameters of formation and clusterization for three classes of bifunctional amphiphiles were calculated using corresponding data for monofunctional amphiphiles. In the example of 2-hydroxycarboxylic acids, α-amino acids, and alkyl amides it was shown that the regarded approach adequately reproduces the parameter values of bifunctional amphiphiles without the direct use of quantum chemical calculations. It exploits rather only the calculated or experimental data existing for corresponding monofunctional amphiphiles. The systematic errors for the description of the thermodynamic parameters of formation and clusterization for bifunctional amphiphiles can be attributed to the incomplete reproduction of the values for the increments of intra- and intermolecular interactions between the functional groups in the molecules of bifunctional alkanes and the corresponding values of the increments for monosubstituted alkanes. These errors can be taken into account using an additive correction. Consideration of this correction allows the assessment of the thermodynamic parameter values of formation for 2-hydroxycarboxylic acids, α-amino acids, and alkyl amides with the following values of standard deviations: 0.01, 0.03, and 0.02 kJ/mol for enthalpy; 0.88, 0.50, and 1.16 J/(mol·K) for absolute entropy; and 0.31, 0.29, and 0.37 kJ/mol for Gibbs’ energy, respectively. The values of the thermodynamic parameters of clusterization per one monomer molecule of 2D films for the considered bifunctional amphiphiles are estimated with deviations in the range of 0.10–0.61 kJ/mol, 1.96–2.99 J/(mol·K), and 0.03–0.87 kJ/mol for clusterization enthalpy, entropy, and Gibbs’ energy, respectively.