The dielectric, refractometric, and volumetric properties were systematically investigated for eight binary systems containing two structurally related ketones (methyl isobutyl ketone and mesityl oxide) and four glycols over the entire composition range at 298.15 and 101 kPa. The selected glycols were (1,3-butylene glycol, pentamethylene glycol, diethylene glycol, and triethylene glycol). The experimental data were analyzed using different approaches in terms of intermolecular interactions between the constituent molecules through excess parameters of different physical quantities. The excess parameters confirm the formation of multimer structure during the mixing process. In addition, the refractive index deviations were calculated in terms of volume fraction. Based on the Iglesias-Reis approach, the influence of the interactions in excess Helmholtz energy and excess permittivity from total interactions follow the same order 1,3BG > DE > PG > TEG for their mixtures with the ketones. All the excess Kirkwood correlation factors (giE) are negative but very small for the mixtures. Thus, the Kirkwood correlation factors for binary mixtures (g12) are not very far from the ideal behavior, and therefore, the dipoles preferentially oriented parallel interrupted for some extent by the mixing process. The Redlich–Kister type polynomial equation was used to fit the experimental excess parameters.