Conformational mobilities of the units and host–guest complexation with n-octyltrimethylammonium hexafluorophosphate of the synthesized perbenzylated pillar[5]arenes were studied. The formed complex was confirmed by proton nuclear magnetic resonance spectroscopy and mass spectral analysis. Hydroxylated pillar[5]arene-based amphiphiles were synthesized by a co-cyclization strategy followed by catalytic hydrogenation. This approach unlocks the synthesis and the design of a wide range of structural manipulations to these amphiphilic pillararenes.