ETHNOPHARMACOLOGICAL RELEVANCE: Xinbao pill (XBP) is a renowned Chinese patent medicine, primarily efficacious in warming and nourishing the heart and kidneys, supplementing Qi to boost Yang, and promoting blood circulation to remove blood stasis. XBP has been utilized for the treatment of chronic heart failure (CHF) for nearly 30 years, but the lack of clarity regarding the active ingredients of XBP against CHF has hindered its clinical application and further promotion. AIM OF THE STUDY: To comprehensively elucidate the efficacy-specific ingredients and potential mechanism of XBP against CHF. METHODS: The efficacy, chemical profiling and pharmacokinetics of XBP was assessed in a CHF model rat. The anti-CHF mechanism of the mixture of the likely active ingredients was clarified by targeted metabolomics and western blotting analysis. RESULTS: XBP alleviated CHF by enhancing cardiac function, reducing NT-pro BNP, mitigating myocardial damage and degrading extracellular collagen. Following XBP administration, ginsenosides exposed relatively abundant in sham or CHF rats. Ginsenoside Rg1 and notoginsenoside R1 showed downward trends in AUC CONCLUSIONS: Our research provides valuable insights that ginsenoside Rg1, ginsenoside Rg2 and notoginsenoside R1 may constitute the anti-CHF active ingredients of XBP for facilitating mitochondrial homeostasis by the suppression of heme synthesis to increase succinyl CoA.