The components of saliva are closely related to the corresponding components in blood. Using saliva instead of blood for detection can greatly reduce analysis time, limitation and potential safety hazard, thus it is of great importance to clinical research and control of drugs. In this work, combined with a portable Raman spectrometer, quantitative detection of pioglitazone hydrochloride (an oral hypoglycemic drug) in saliva has been realized by surface-enhanced Raman spectroscopy (SERS). With this method, the characteristic Raman peaks for pioglitazone hydrochloride can be easily observed. Furthermore, the SERS method can be used to quantitatively detect the pioglitazone hydrochloride in saliva. The concentration of pioglitazone hydrochloride is linearly correlated to its Raman intensity with a coefficient of determination (R2) of 0.992 3, and the minimum detectable concentration can be as low as 10 μg·L-1.