Terahertz time-domain spectroscopy (THz-TDS) combined with chemometric modeling methods was used to perform quantitative analysis of both active pharmaceutical ingredient (API) and excipient concentrations of multicomponent pharmaceutical mixtures. The THz spectra of ternary mixtures formulated with anhydrous theophylline, lactose monohydrate, magnesium stearate and quaternary mixtures composed of acetaminophen, lactose monohydrate, microcrystalline cellulose and soluble starch were measured using THz-TDS. Two multivariate calibration methods, principal component regression (PCR) and partial least squares (PLS) regression, were employed to correlate THz absorbance spectra with the pharmaceutical tablet concentrations. Both API and excipient concentrations of mixtures were predicted simultaneously, and the PLS method provides better result than PCR method. The correlation coefficients of calibration (Rcal) and validation (Rval) for ternary mixtures’ components, anhydrous theophylline and lactose monohydrate, were all more than 0.98. The Rcal and Rval for quaternary mixtures’ components, acetaminophen, lactose monohydrate, microcrystalline cellulose and soluble starch, were all more than 0. 93, 0.98, 0.63 and 0.86, respectively. Experimental results show that THz-TDS combined with chemometrics is feasible in nondestructive quantitative analysis of multicomponent mixtures, and it can be widely applied in the fields of pharmaceutical analysis and others.