Dielectric studies under various temperature (T) and pressure (p) conditions on five active pharmaceutical ingredients (APIs) with antifungal properties-itraconazole (ITZ), posaconazole (POS), terconazole (TER), ketoconazole (KET), and fluconazole (FLU)-were carried out. We have thoroughly studied the connection between the pressure coefficient of the glass transition temperature (dT(g)/dp) and the activation volume of both relaxation modes (Delta V-a, Delta V-delta d/a') with respect to the molecular weight (M-w) or molar volume (V-m) in these systems. Besides, high pressure data revealed that the time scale separation between alpha- and delta- or alpha'-processes increases with pressure in ITZ and TER. What is more, the activation entropy, which is a measure of cooperativity, calculated from the Eyring model for the secondary (beta)-relaxation in ITZ and POS, increased and decreased, respectively, in the compressed samples. To understand these peculiar results, we have carried out X-ray diffraction (XRD) measurements on the pressure-densified glasses and found that pressure may induce frustration in molecular organization and destroy the medium-range order while enhancing the short-range correlations between molecules. This finding allowed us to conclude that varying molecular spatial arrangement is responsible for the extraordinary dynamical behavior of ITZ, POS, and TER at high pressure.