The phenoxazine class of dyes has found widespread applications in chemistry and biology for more than a century, particularly for lipid membrane studies. Here, we report a general phenomenon on the ensemble spectral stability of traditional phenoxazine class of dyes (nile red, cresyl violet, and nile blue) that exhibit hours-long microstructural transitions reflected through systematic changes of electronic spectra over an hour. Mechanistic investigations reveal that such spectral dynamics of the dyes can be mitigated by tuning microenvironments, where microsolvation plays an underlying role. These microsolvation-induced microstructural changes in a single dye species tend to follow zeroth-order kinetics. The half-life values of such processes systematically vary with solvent hydrogen bonding strength and ionic radius of the dyes' counteranions. In so doing, using a model lipid membrane, we demonstrate that the spectral response of a phenoxazine dye must be utilized appropriately for studying membrane properties. These findings of the phenoxazine class of dyes are of high significance for their careful applications in chemistry and biology.