The sodium chloride (NaCl) salt has been reported to be associated with glucose metabolism. However, the effect of it on non-invasive detection of blood glucose using near-infrared spectroscopy is still an open question. The aim of this study was to investigate this affection through transform background correction analysis two-dimensional (2D) correlation synchronous spectrum and the partial least-squares (PLS) regression. First, the transmittances of glucose aqueous solutions with different NaCl content are collected and the pure water and NaCl aqueous solution are measured as the background. Results show that, the dissolving of NaCl in water changes the amplitude and position of the absorption peak of water. There are two negative peaks in 1 400 and 1 500~1 700 nm corrected spectra of NaCl aqueous obviously and the amplitude of peaks associated with NaCl concentration. That’s because NaCl affect the molecular binding and vibration of water. Then the glucose aqueous solutions without NaCl and with NaCl are corrected by the spectra of pure water and NaCl aqueous solution, respectively. So we get the conclusion that NaCl also affect the combination of glucose and water molecules. And the two-dimensional correlation spectroscopy analysis is performed under the perturbation of glucose concentration. The slice spectra of synchronous correlation spectra show that, the adding of NaCl weakens the spectral variation due to glucose concentration change in the wavelength of 1 400 and 1 520~1 700 nm. Finally, the partial least square (PLS) regression models were built to quantitatively conduct the influence of NaCl on glucose prediction accuracy. Comparison results showed that, NaCl molecule in aqueous solution will deteriorate the model accuracy, where root mean square error of prediction increases with the NaCl content; the mean difference of predicted glucose concentration between models based on glucose aqueous solutions with NaCl and without NaCl, is linear with NaCl concentration in samples.