Guided mode resonance (GMR) sensors have emerged as transformative tools in sensing technology, offering exceptional sensitivity, selectivity, and real-time, label-free detection capabilities across diverse applications, including medical diagnostics and environmental monitoring. Their miniaturization potential, cost-effective manufacturing, and wide dynamic range make GMR sensors highly versatile and commercially attractive. In this study, we present an optofluidic GMR platform tailored for real-time analysis of biomolecular interactions without the need for optical labels. The platform integrates a custom-built inverted microscopy system, a high-resolution multispectrometer setup with a spectral resolution of 0.15 nm, and an automated multipump fluid control system, enabling precise and efficient monitoring of binding kinetics between biomolecules. Key outcomes include a refractive index sensitivity of 201.73 nm/RIU and a demonstrated detection limit of 0.15 ng/mL for IgG protein, emphasizing the platform's suitability for highly sensitive biodetection applications. Additionally, the automated flow methodology enhances efficiency and reproducibility by streamlining chip preparation, ligand/analyte incubation, and postexperiment cleaning, minimizing manual intervention and human error. The self-cleaning feature ensures contamination-free operation, facilitating seamless multiuse experiments. Furthermore, we determined the association constant during the binding of protein A/G and IgG, underscoring the platform's applicability to real-time binding kinetics studies. These results establish our optofluidic GMR platform as a robust and precise tool for advancing the understanding of complex biomolecular processes.