The depolarization property of a biomedium with anisotropic biomolecule optical scattering is investigated theoretically. By using a simple ellipsoid model of a single biomolecule, the scattering fields and Mueller matrices are derived from fundamental electromagnetism theory. The biomedium is modeled as a system of uncorrelated anisotropic molecules. On the basis of a statistical model of anisotropic molecular distribution, the scattering depolarization of the biomedium is investigated. Simulated results of the molecular shape and orientation dependent single scattering depolarization $D_1$ and the double scattering depolarization $D_2$ are reported. The $D_2$ contribution is found to be more important for higher-density scattering media. The depolarizations of the forward single and double scattering of a model cell membrane are simulated and discussed. The fitting to a single tetra-methylrhodamine-labeled lipid molecule’s anisotropic imaging experiment has demonstrated that large depolarization arises for the membrane to which the fluorescence emitting molecule is attached. This theory can provide a simulation analysis tool for investigating the scattering polarization/depolarization effect and the photon density wave transport property of a highly scattering biomedium.