Control of the self-assembly and disassembly at the molecular level has become a subject of increasing activity. The supramolecular assembly between a photoswitchable azobenzene-containing surfactant, AzoC10, and α-cyclodextrin that combines photochemistry and host–guest chemistry for a stimulus-responsive vesicle has been recently reported. To clarify the role of photoisomerization in the reversible assembly and disassembly, we present in this work atomistic molecular dynamics simulations of the host–guest complexation of AzoC10 with α-cyclodextrin. The results of simulation reveal that both cis- and trans-AzoC10 form the inclusion complexes with α-CD, but the binding modes are rather different. The azobenzene moiety of trans-AzoC10 is included at the center of the cavity of α-CD, whereas one of the phenyl rings of cis-AzoC10 is exposed to water and the other is included in the cavity of α-CD. The shuttling motion of α-CD over the long alkyl chain of cis-AzoC10 is observed in the simulations. The potentials of mean force calculated for AzoC10 to pass through the cavity of α-CD show that the host–guest assembly is basically downhill for trans-AzoC10, but an energy barrier has to be overcome for cis-AzoC10 to complex with α-CD.