Despite the growing research in CaTiO₃ as a novel high-temperature oxide thermoelectric material, effects of various elements doping on the microstructure and thermoelectric performance of CaTiO₃ have not been fully understood. Here, a combination of hydrothermal synthesis and vacuum hot-press sintering techniques was employed to fabricate polycrystalline bulks of CaTiO₃ doped with six elements: Cr, Nb, Eu, Dy, Ce, and La. Cr doping resulted in substantial precipitation of nanoscale Cr phases, leading to a severely compromised power factor and a ZT of only 0.012 at 983 K due to insufficient donor element concentration in the matrix. Incorporating Eu as a donor carrier in the matrix is proved ineffective, resulting in a marginal ZT enhancement of 0.141 at 1031 K. Nb doping resulted in the formation of micrometer-scale Nb phases with high thermal conductivity, leading to an elevation in thermal conductivity. However, the relatively higher Nb concentration in the matrix provided carriers, resulting in a noticeable ZT improvement to 0.263 at 1013 K. On the contrary, Dy, Ce, and La doping exhibited remarkable dual functionality as donor dopants and point defects, thereby significantly enhancing the power factor and concurrently reducing the lattice thermal conductivity. These improvements were achieved through efficient manipulation of carrier concentration and implementation of phonon scattering. As a result, the thermoelectric figure of merit (ZT) reached 0.357, 0.398, and 0.329 at 1031 K for Dy, Ce, and La-doped CaTiO₃ bulks, respectively. These values represent an extraordinary improvement of 296%, 342%, and 265%, respectively, as compared to that of the pristine CaTiO₃ (0.096 @1031 K). Notably, Dy-doped samples exhibited significantly reduced lattice thermal conductivity and comparatively higher power factors over the entire temperature range. Regulating Dy content and enhancing the second phase at grain boundaries enabled the decoupling of electrical and thermal transport properties, potentially surpassing the current ZT record of CaTiO₃. This study provides valuable insights into the relationships among composition, structure, and performance in CaTiO₃ doped with various elements, offering theoretical support for high-temperature thermoelectric applications.