The rapid quantification method of glucose aqueous solution was established by using the Fourier transform infrared spectroscopy (FTIR) and attenuated total reflection (ATR). Model optimization and wavenumbers selection was investigated based on Savitzky-Golay (SG) smoothing. For the whole spectral collecting region 4500-600 cm-1 and the fingerprint region 1600-900 cm-1, Partial least squares (PLS) models without and with SG smoothing were established respectively. The optimal model was on the fingerprint region with SG smoothing of 1st order derivative, 2nd degree polynomial and 73 smoothing points, PLS factor, RMSEP, RP, were 4, 0.331 mmol/L, 0.999 respectively. Based on 19 absorption peaks of the subtracted spectra of glucose aqueous solution for de-ionized water, all possible wavenumber combinations were used to establish discrete multiple linear regression (MLR) models respectively, the optimal wavenumbers combination was 3084, 1034, 991 (cm-1), RMSEP and RP were 0.459 mmol/L, 0.997 respectively. It could provide valuable references for designing spectrophotometer system in special spectrometer and further for glucose analysis of the complex system. To get the stable prediction results, all models and results here were obtained based on the average data on 50 different divisions of calibration set and prediction set.