Herein, we reported a new strategy based on self-assembly chemistry for chiral discrimination of glucose on a new S-mandelic acid-appended calix[4]arene (S-MC4) modified nanostructure, which exhibits macroscopic chiral preference for d-glucose via contact angle measurements (CA). The proposed macroscopic chiral device displays rapidly remarkable specificity and is convenient to use, which should be suitable for diagnostic purposes, nanomedical applications, etc.