A new insight is presented in the fabrication of a simple chiral electrochemical sensor for tyrosine enantiomers which are the biomarkers of depression. The conductive sensor is based on modifying the glassy carbon electrode with two consecutive layers namely multi-walled carbon nanotubes-ionic liquid crystal (CNT+ILC) and 18-crown-6 (CW); GC/(CNT+ILC)/CW. CW is introduced for the first time as an excellent receptor for the chiral recognition of Ty enantiomers due to its perfect host-guest size matching principle. On the other hand, beta-cyclodextrin (beta-CD) does not recognize Ty enantiomers as its cavity size was larger, and needs extra modifications. Moreover, itwas observed due to the opposite steric configurations of the Ty enantiomers, CW preferably forms strong complexes with L-Ty compared to D-Ty enantiomers, resulting in significantly noticeable electrochemical differences in their peak current responses with ratio of (L-Ty to D-Ty) about 3.09. TheGC/(CNT+ILC)/CW showed excellent current responses for the electrochemical analysis of L-Ty and D-Ty enantiomers in the concentration ranges of 0.01-60 mu mol L-1 and 0.09-60 mu mol L-1 with low detection limit values of 1.42 nmol L(-1)and 9.36 nmol L-1, respectively. The practical impact of the sensor was illustrated in accurate determination of the percentage of enantiomers in Ty racemic mixture. Moreover, the electro-oxidation of AA, UA, and L-Ty in their ternary mixture was successfully achieved to three well-separated peaks using the GC/(CNT+ILC)/CW sensor. (c) 2019 The Electrochemical Society.