An N,N-Dimethylamine ethylimino-appended triazole-linked calix[4]arene conjugate, L, has been synthesized and characterized, and its Cd 2+ complex has been isolated and characterized. The structure of [CdL] was established by computational calculation using B3LYP/LANL2DZ. Time-dependent density functional theory calculations were performed to demonstrate the electronic properties of [CdL]. This highly fluorescing [CdL] has been used to recognize Cys selectively among the 20 naturally occurring amino acids. [CdL] exhibits a minimum detection limit of 58 ppb for Cys, with reusability and reversibility being imparted to the system during sensing. Thus, the sensing of Cys was well demonstrated using various techniques, viz., fluorescence, absorption, visual color change, electrospray ionization MS, 1H NMR, and live cell imaging experiments. © 2012 American Chemical Society.