Among the numerous gatekeepers, peptides have attracted much interest due to their specific targeting, cell penetrating, endo-/lysosomal escaping, and enzymatic degrading capabilities. Recently, we developed peptide gatekeepers with turn structures that were triggered to release via stimuli-responsive conformational conversion. In this report, to extend the utilization of stimuli-responsive peptide gatekeepers on the surface of MSNs, we prepared α-helical peptide gatekeepers with a capability for stimuli-responsive conformational conversion on the surface of mesoporous silica nanoparticles. The stimuli-responsive α-helical peptide gatekeepers controlled the release of entrapped drugs triggered by GSH addition and consequential conformational conversion. Furthermore, the nanoparticles efficiently disrupted the liposome membranes. Therefore, stimuli-responsive α-helical peptide gatekeepers would be useful for the construction of mesoporous delivery vehicles with enhanced therapeutic efficacy via membrane disruption.