In this study, the dissociation mechanism of self-assembled cyclic peptides (CPs) has been investigated using classical/steered molecular dynamics simulations combined with umbrella sampling techniques in a polar and a nonpolar solvent. The stability of cyclic peptide nanotubes (CPNTs) with different surface polarity, {cyclo-[(n-Trp-L-Leu)(4)]}(8) Ala-L-Glu-D-Ala)(2)]}(8), are explored in detail. It is observed from the results that the CPNTs are less dynamic, in the nonpolar:. solvent than in the polar solvent. The dissociation of CPs from a lower oligomeric form is achieved by gradual breaking of. interactions, requiring relatively little force. In higher oligomeric CPNTs, the dissociation takes place by collective breaking of interactions with significantly higher force. During the dissociation process, the tendency for collective breaking of various intermolecular interactions increases from the terminal to the core of the CPNT The breaking of backbone-backbone hydrogen bonding is the critical point in the dissociation of CPs which is followed by the annihilation of various side chain-side chain interactions. The polarity of the solvent plays a decisive role in the dissociation mechanism of self-assembled CPs. It is evident from the calculated free energy of binding values that the overall stability of CPNT is higher in the nonpolar solvent than in the polar solvent.