Stem cells exhibit unique characteristics of self-renewal and differentiation, the ability to produce unlimited daughter cells and transform into various cell types, respectively. Current biochemical-based analytical techniques for monitoring cellular behaviors are accurate, yet destructive, limiting their use as end-point analyses. In order to continuously monitor the same population of the cells, a novel multi-modal system that encompasses both quartz crystal microbalance (QCM) and electrochemical impedance spectroscopy (EIS), as well as having an optical visualization capability, has been developed to characterize physioelectrochemical changes of the cells during self-renewal and differentiation in real-time. Human induced pluripotent stem cells (IPSCs) were utilized to validate the functionality of the device. An equivalent circuit model was then designed from experimental impedance data to correlate physical changes of the cells to electrical circuit components throughout the progression of stem cell self-renewal and differentiation. Overall, the combination of the quantitative information from the device and electrical circuit modeling collectively offers a means for an in-depth understanding of physical processes underlying cellular behaviors to determine the states of stem cell self-renewal and differentiation.