The mid-infrared (mid-IR) anisotropic optical response of a material probes vibrational fingerprints and absorption bands sensitive to order, structure and direction dependent stimuli. Such anisotropic properties play a fundamental role in catalysis, optoelectronic, photonic, polymer and biomedical research and applications. Infrared dual-comb polarimetry (IR-DCP) is introduced as a powerful new spectroscopic method for the analysis of complex dielectric functions and anisotropic samples in the mid-IR range. IR DCP enables novel hyperspectral and time-resolved applications far beyond the technical possibilities of classical Fourier-transform IR (FTIR) approaches. The method unravels structure–spectra relations at high spectral bandwidth (100 cm–1) and short integration times of 65 µs, with previously unattainable time resolutions for spectral IR polarimetric measurements for potential studies of noncyclic and irreversible processes. The polarimetric capabilities of IR-DCP are demonstrated by investigating an anisotropic inhomogeneous free-standing nanofiber scaffold for neural tissue applications. Polarization sensitive multi-angle dual-comb transmission amplitude and absolute phase measurements (separately for ss-, pp-, ps- and sp-polarized light) allow the in-depth probing of the samples’ orientation dependent vibrational absorption properties. Mid-IR anisotropies can be quickly identified by cross-polarized IR-DCP polarimetry.