Background: Berberine has been verified to protect the heart from ischemia/reperfusion injury through animal experiments. However, the cardioprotective properties of berberine have not been established fully. This study was aimed at investigating whether berberine is cardioprotective in vivo and in vitro. Methods: In the cardiomyoblast cells, the autophagosomes were observed by immunostaining. The apoptosis was detected by a flow cytometry. Beclin-1, LC3-II/I, adenosine monophosphate-activated protein kinase (AMPK), and mTOR in cardiomyocytes were detected by Western blot. Next, one hundred patients, who were undergoing percutaneous coronary intervention (PCI), were randomly assigned to the berberine group (n = 52) or control group (n = 48). Berberine was administered on them postoperatively. Their plasma was then analyzed for CRP, TNF-alpha and IL-6. Results: In the cardiomyoblast cells, berberine reduced the autophagy and apoptosis induced by NaH2PO4. At the same time, berberine increased the activation of p-AMPK and inhibited the activation of p-mTOR induced by NaH2PO4. in vivo, berberine significantly reduced the levels of CRP, TNF-alpha and IL-6 in the patients' plasma. Conclusion: It was concluded that berberine therapy reduced myocardial injury partly by reducing myocardial autophagy and apoptosis through the AMPK/mTOR pathway.