Our previous work demonstrated that Cr2Ge2Te6based compounds with a layered structure and high symmetry are good candidates for thermoelectric application. However, the power factor of only ∼0.23 mW/mK2in undoped material is much lower than that of conventional thermoelectrics. This indicates the importance of an electronic performance optimization for further improvements. In this work, either Mn- or Fe-substitution on the Cr site is investigated, with expectations of both carrier concentration control and band structure engineering. First-principle calculations indicate that an orbital hybridization between d orbitals of the doping atom and the p orbital of Te significantly increases the density of states (DOS) around the Fermi level. In addition, it is found that Mn doping is more favorable to improve the electrical properties than Fe doping. By tuning the carrier concentration via Mn doping, the peak power factor rises rapidly from 0.23 mW/mK2to 0.57 mW/mK2at 830 K with x= 0.05. Combined with the intrinsic low thermal conductivity, Cr1.9Mn0.1Ge2Te6displays a decent zTof 0.63 at 833 K, a 2-fold value as compared to that of the undoped sample at the same direction and temperature.