To test the biocompatible character of room-temperature ionic liquids (ILs), the interaction of various ILs with biological membrane (biomembrane) models was studied in this work. Dioleoyl phosphatidylcholine (DOPC) adsorbed I on a mercury (Hg) electrode forms an impermeable defect-free rnonolayer which is a well established biomembrane model, prone to be studied by electrochemical techniques. We. have monitored the modifications of the Hg supported monolayer caused by ILs using rapid cyclic voltammetry (RCV), alternating current voltammetry (ACV), and electrochemical impedance spectroscopy (EIS). A series of imidazolium-based ILs were investigated whose interaction highlighted the role of anion and lateral side chain of cation during the interaction with DOPC monolayers. It was shown that the hydrophobic and lipophilic character of the IL cations is a primary factor responsible for this interaction. Hg-supported monolayers provide an accurate analysis of the behavior of ILs at the interface of a biomembrane leading to a comprehensive understanding of the interaction mechanisms involved. At the same time, these experiments show that the Hg-phospholipid model is an effective toxicity sensing technique as shown by the correlation between literature in vivo toxicity data and the data from this study.