Polycrystalline oxide materials exhibit semiconductor properties due to grain boundary (GB) and grain characteristics, which enrich the variety of applications. However, how to regulate the energy band structure of grains and the potential barriers at GBs through defect engineering is crucial to achieve a high performance electronic device. Herein, it is found that Fe3+ ions can change the grain energy band structure of CaCu3Ti4O12 (CCTO) materials, which enhances the linearization of the resistance–temperature curve (lnρ–1000/T) in the high temperature region. First principles calculation indicates that Fe3+ doping narrows the forbidden band and induces new impurity energy levels in the forbidden band, which matches the conclusion that the resistivity–temperature dependence of grains shifts toward the low-temperature region as derived from impedance spectroscopy. This shift results in no monotonic variation in grain resistivity within the application temperature region, thus enhancing the linearity of the lnρ–1000/T curve of CCTO materials in the high temperature region. In addition, Fe3+ ions can modulate the activation energy of CCTO materials in a wide range by changing the activation energy of GBs, which broadens the temperature range of CCTO. The significance of this work lies not only in achieving linearization of CCTO materials for high temperature thermistor application, but more importantly, the method presented here provides an avenue for the study of polycrystalline semiconductor materials.