To explore the interactions of self-oriented glucose toward organic species, we prepared a glucose-modified infrared (IR) chemical sensor and examined its performance in the detection of compounds bearing carboxylic acid functional groups. Using a two-layer modification method, we chemically bonded glucose to the surface of an IR sensing element. The immobilized glucose moieties exhibited the ability to assemble into a chemical form similar to that of the cyclodextrins (CDs) such that they could trap targeted molecules. This modified sensing phase displayed an analysis capability similar to that of CDs, but without the problems encountered attempting to maintain the activity of the latter. From a systematic examination of three classes of structural analogs of acids, we found that the behavior of the glucose-modified sensing phase was similar to that of a CD-modified sensing phase. In terms of quantitative detection, we obtained an average regression coefficient of approximately 0.996 for the analytical signals of the examined compounds at concentrations less than 20 mg/L. The linearity of the standard curves was related to the detection time: the shorter the detection time, the greater the linearity. Defined as three times the noise level, we obtained detection limits of a few hundred parts per billion (μg/L) for the determination of high-polarity compounds using our glucose-modified sensing phase.