Nanoplastics are a growing environmental concern due to their potential to disrupt cellular functions. Understanding how these particles interact with cell membranes is crucial for assessing their biological effects. In this study, we present a label-free, quantitative method─Single Cell Deformation Plasmonic Imaging (SCDPI)─to measure real-time membrane interaction dynamics at the single-cell level. By examining both fixed and live cells, we characterized the binding behaviors of nanoplastics with varying sizes, surface chemistries, and materials. Our findings show that nanoplastic binding induces cell membrane deformation ranging from a few to tens of nanometers, depending on nanoplastic type and concentration (0-250 μg/mL), influencing membrane-surface interactions. This work provides new mechanistic insights into nanoplastic-cell interactions, demonstrating the potential of SCDPI as a powerful tool for evaluating the cellular impacts of environmental pollutants.