Density functional theory calculations and Boltzmann transport theory are used to simulate the thermoelectric properties of SrTiO3 ceramics with two-dimensional electron gas grain boundaries (GBs). This material can achieve a large thermoelectric figure of merit (ZT > 1 at room temperature) by utilizing quantum confinement and energy filtering at GBs. The latter causes the ZT value to reach a maximum before decreasing with an increasing GB barrier height. The optimum barrier height was approximately 0.06 eV higher than the Fermi energy of the grain interior. Our results may aid the design of materials with environmentally benign thermoelectric oxides.