The performances of tetracycline based cation selective polymeric membrane electrodes of many sets with different plasticizers were investigated as the selectivity of ion-selective electrodes and optodes are greatly influenced by membrane solvent and also controlled by plasticizers. The membrane 1 with Bis(2-ethylhexyl) sebacate (DOS) and additive shows good potentiometric performance toward Ca2+ (slope: 27.8 mV per decade; DL: -4.52) including selectivity. Contrastingly, membrane 4 with Dibutyl phthalate (DBP) shows near-Nernstian response, it has also shown the best measuring range and detection limit for Ca2+ (29.5 mV and -5.10) and Mg2+ (24.4 mV and -5.04) and the least selectivity has been also observed between Ca2+ and Mg2+. When the membrane 1 and 4 were used together to flow system, we could determine the concentration of Ca2+ and Mg2+, simultaneously.