Salvianolic acid B (Sal B), one of the chief water-soluble constituents in Radix Salviae Milthiorrhizae, has often been reported to possess considerable cardiovascular regulatory effects. However, the underlying biochemical and cellular mechanisms of its cardioprotection remain unclear. This study was designed to evaluate the role of Sal B regulation in L-type Ca channel currents (I) and cell contractility in rat cardiomyocytes and hERG K channels expressed in HEK293 cells with the patch-clamp and Ca imaging techniques to clarify its underlying cardioprotective mechanisms. Exposure to Sal B blocked I with IC of 2.07 × 10 M, shifted the curves of current and voltage upwards, shifted the curves of activation and inactivation to the left, and significantly inhibited the amplitude of the cell shortening, but the regulatory effects of Sal B on the expressed rapidly activating delayed rectifier potassium current (I) did not reach a significant level. These results indicate that the cardioprotective mechanisms of Sal B may be related to the attenuation of calcium overload by directly inhibiting I and consequently decreasing myocardial contractility without causing drug-induced long QT syndrome (LQTS).