The platform includes engineered beta-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse, which are coupled with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Demonstrated application was the observation of in vivo beta-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Abdominal imaging windows (AIW) can extend in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in the ability to study beta-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of beta-cell physiology in the endogenous islet niche.