Background: Electrophysiological sensing of cardiomyocytes (CMs) in optogenetic preparations applies various techniques, such as patch-clamp, microelectrode array, and optical mapping. However, challenges remain in decreasing the cost, system dimensions, and operating skills required for these technologies. Objective: This study developed a low-cost, portable impedance plethysmography (IPG)-based electrophysiological measurement of cultured CMs for optogenetic applications. Methods: To validate the efficacy of the proposed sensor, optogenetic stimulation with different pacing cycle lengths (PCL) was performed to evaluate whether the channelrhodopsin-2 (ChR2)-expressing CM beating rhythm measured by the IPG sensor was consistent with biological responses. Results: The experimental results show that the CM field potential was synchronized with external optical pacing with PCLs ranging from 250 ms to 1000 ms. Moreover, irregular fibrillating waveforms induced by CM arrhythmia were detected after overdrive optical pacing. Through the combined evidence of the theoretical model and experimental results, this study confirmed the feasibility of long-term electrophysiological sensing for optogenetic CMs. Conclusion: This study proposes an IPG-based sensor that is low-cost, portable, and requires low-operating skills to perform real-time CM field potential measurement in response to optogenetic stimulation. Significance: This study demonstrates a new methodology for convenient electrophysiological sensing of CMs in optogenetic applications.