In the fabrication of cardiac tissue, an important factor is continuous measurement of its contraction features. A module that allows for a dynamic system capable of noninvasive and label-free monitoring of the contraction profile under administering chemicals and drugs is highly valuable for understanding accurate tissue mechanobiology. In this research, we have successfully demonstrated the use of surface plasmon resonance (SPR) technology for the first time to characterize the contractility of cardiac cells in response to Blebbistatin and ATP drug exposure in real tme. An optimal flow rate of 10 μL/min was selected for a continuous flow of warm media,and 10 μM drug administration effect was detected with high spatiotemporal sensitivity on contracting cardiomyocytes. Our drug screening has identified the source of the SPR periodic signal to be direct cell contraction rather than action potentials or calcium signaling. Per our results, SPR has high potential in applications in least-interference real-time and label-free tissue characterizations and cellular properties analysis from a functional and structural point of view.