A new aldehyde calixarene (C4AH) was synthesized efficiently to give a yield of 90 % and was used to form self-assembled monolayers (SAMS) by means of click chemistry to give a highly selective wettability and impedance sensor for arginine (Arg). The success of the C4AH functional interface and Arg-responsive events were confirmed by contact-angle (CA) measurements and electrochemical impedance spectroscopy (EIS). Furthermore, the C4AH functional interface can be used as wettability-responsive cycles at least eight times. This type of sensor operates on the principle that Arg has a high pKa value of 12.48, and is able to form strong hydrogen bonds with aldehyde selectivity, which results in a significant CA change. The proposed wettability-sensing devices display a remarkable specificity, intuitiveness, and convenience, which should be suitable for the production of arginine recognition chips that can be used in the fields of biology and medical science.