We describe the detection of glucose based on a liquid-ion gated field-effect transistor configuration in which enzyme-functionalized polypyrrole nanotubes are employed as the conductive channel. First of all, carboxylated polypyrrole nanotubes (CPNTs) were successfully fabricated by the chemical polymerization of an intrinsically functionalized monomer (pyrrole-3-carboxylic acid, P3CA) without degradation in major physical properties. The CPNTs possessed not only well-defined functional groups but also electrical properties comparable to nonsubstituted polypyrrole. Importantly, the carboxylic acid functional group can be utilized for various chemical and biological functionalizations. A liquid-ion gated FET sensor was readily constructed on the basis of the chemical functionality of CPNTs. In the first stage, the CPNTs were immobilized onto a microelectrode substrate via covalent linkages. It was noteworthy that the covalent immobilization allowed high-quality contact between the nanotubes and the microelectrodes in the liquid phase. The second stage involved the covalent binding of glucose oxidase (GOx) enzyme to the nanotubes. The covalent functionalization generally provides excellent enzymatic activity and thermal stability. The fabricated FET sensor provided real-time response (an increase in source-drain current) and high sensitivity toward the various concentrations (0.5-20 mM) of glucose. The enzymatic reaction product, hydrogen peroxide, played pivotal roles in modulatincy the charge transport property of CPNTs.