The application of ionic liquids (ILs) in many industrially relevant processes provides an urgent need to better understand their molecular interactions with biological systems. A detailed understanding of the cytotoxicity mechanism of ILs can be helpful in facilitating the molecular design of nontoxic ILs. Using coarse-grained molecular dynamics (MD) simulations, we investigate the effects of imidazolium-based ILs on several lipid bilayer morphologies. Our results demonstrate that the asymmetric insertion of IL cations into one side of a lipid bilayer leaflet enhances the leaflet strain, which upon reaching a critical value triggers a morphological disruption in the bilayer. Consistently, the bending modulus of the bilayer is reduced by 1 to 2 orders of magnitude relative to that of an IL-free planar bilayer prior to the disruption event. Our results suggest that ILs that can easily insert into the lipid bilayer without diffusing across or inducing lipid flip-flop can be more disruptive to a lipid biomembrane.