Manipulating the π-electron magnetism of single-molecule junctions is an effective means to improve the electronic and spin-polarized thermoelectric transport properties. Here, using the density functional theory combined with the nonequilibrium Green's function method, we demonstrate that the electronic conductance (σ) of molecular junctions (MJs) can be significantly enhanced by organic radicals due to the shifting of resonant states. Moreover, we find that the spin-dependent quantum interference (SDQI) effects can be largely influenced by organic radicals. The SDQI effects result in nearly 100% spin filtering efficiency in open-shell molecules and greatly enhance the Seebeck coefficients. As a result, the thermoelectric performances of open-shell MJs at room temperature are greatly improved through the combined effects of radicals and SDQI. In particular, the maximum ZTsp in the four radical junctions reaches up to 36.5. Our results show great potential for improving thermoelectric performance through the utilization of quantum interference and organic radical.