Thermoelectric effect enables direct conversion between thermal and electrical energy and provides an alternative route for power generation and refrigeration. Hereby it is important to find materials with a high thermoelectric performance. In this sense, in the present work, we study the behavior of the thermoelectric properties of functionalized graphene grain boundaries by employing non-equilibrium Green’s Functions formalism combined with density functional tight-binding theory (NEGF-DFTB) approach. Our results show that H and O ad-atoms affect the phonon and electron transport properties of the grain boundaries but the thermoelectric figure of merit is slightly reduced. However, grain boundaries functionalized with nitrophenyl molecules improve the thermoelectric behavior. We have also found that physisorbed molecules do not alter their transport properties. We expect our results to shed light on the potential of 2D materials for engineering highly efficient nanoscale thermoelectric devices.