Mueller polarimetry provides a comprehensive characterization of tissue-induced polarization changes through the measurement of the 4 × 4 Mueller matrix, offering quantitative insight into tissue structural anisotropy and depolarization properties. By exploiting polarized light, this technique reveals origin of observed contrasts and gives diagnostic information beyond that of conventional intensity-based methods. While challenges such as strong depolarization and spatial heterogeneity of tissues have historically limited the clinical adoption of the technique, recent advancements in polarimetric instrumentation, theoretical modeling, and machine learning-driven analysis are paving the way for practical medical applications. This chapter reviews the Stokes–Mueller formalism, Mueller matrix decomposition algorithms, experimental implementation of Mueller polarimeters, and emerging applications in optical biopsy, digital histology, and surgical guidance.