In this study, the effect of post-deposition tetrafluoromethane (CF4) plasma treatment on the physical and electrical characteristics of an In2TiO5 based electrolyte-insulator-semiconductor (EIS) sensor was investigated. Post-deposition CF4 plasma treatment typically improved the crystalline structure and repaired dangling bonds at the grain boundaries. We used the newly fabricated device to detect several ions, such as sodium and potassium, which are essential for many biological processes. The as-deposited and CF4 plasma treated In2TiO5 sensing window with an EIS structure was also able to detect the pH of a solution, different alkali ions (Na+ and K+), glucose, and urea. The sensing membrane after a 60-sec CF4 plasma treatment displayed improved biosensing characteristics, such as higher sensitivity (59.64 mV/pH), better drift rate, and a smaller hysteresis voltage of approximately 0.424 mV/h. The In2TiO5 sensing membrane treated with CF4 plasma is a promising material for use in EIS biosensing applications.