The objective of this study was to prepare solid dispersions consisting of baicalein and a carrier with a low glass transition/melting point (Pluronic F68) by spray freeze drying (SFD). We compared these powders to those produced from the conventional solvent evaporation method. In the SFD process, a feeding solution was atomized above the surface of liquid nitrogen following lyophilization, which resulted in instantaneously frozen microparticles. However, solid dispersions prepared by the solvent evaporation method formed a sticky layer on the glass flask with crystalline baicalein separated out from the carrier. The powder samples were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), surface area measurement, differential scanning calorimetry, and Fourier transform infrared spectrometry. SEM and PXRD results suggested that the majority of baicalein in the SFD-processed solid dispersion was in the amorphous state, which has a higher specific surface area than pure baicalein. However, the majority of baicalein was recrystallized in the solid dispersion at the same composition prepared by the solvent evaporation method, which showed a similar dissolution rate to the physical mixture. SFD product was physically and chemically stable after being stored at 40°C with low humidity for 6 months. After enzyme hydrolysis, baicalein in the SFD product displayed a significantly shorter T max and higher C max than pure baicalein after oral dosing. The relative bioavailability of the SFD product versus pure baicalein determined by comparing the AUC0-12 was 233%, which demonstrated the significantly improved oral bioavailability of baicalein produced by the SFD technique.