Shengxian Decoction (SXT), a classic Traditional Chinese Medicine (TCM) prescription, consists of five TCMs: Astragali Radix, Anemarrhenae Rhizoma, Bupleuri Radix, Platycodonis Radix (PG), and Cimicifugae Rhizoma. SXT has been demonstrated to show good therapeutic effects on the cardiovascular system. A metabolomic approach was applied to study its therapeutic mechanisms and the synergistic properties of PG. UPLC-Q-TOF/MS based metabolomic profiling was adopted to assess the intervention effects of SXT, SXT-PG (SXT lacking PG) and PG, on chronic heart failure (CHF) rats. Betaloc was used as a positive control drug. A supervised discriminant technique (PLS-DA) was used to visualize the difference in global metabolic profiles within all experimental groups. Some significantly changed metabolites, such as carnitines, long-chain fatty acids and sphinganines, were identified, and the biochemical alterations of these were related to the disturbance in serum metabolic profiling of CHF rats. Furthermore, the metabolomics study demonstrated that the administration of SXT, but neither SXT-PG or PG alone, gave satisfactory curative effects on CHF through partially regulating the perturbed metabolic pathways. These observations were demonstrated by histopathological, electrocardiogram and serum enzymatic investigations. All these results supported the TCM theory that PG possesses synergistic properties which promote the synergized herbs in SXT in CHF rats. Overall, this paper demonstrates that metabolomics offers opportunities to understand the therapeutic mechanisms and synergistic properties of TCM.