A thermally comfortable indoor environment is critical for ensuring the health and productivity of the occupants. This study aims to develop a combined CFD-based genetic algorithm and human body thermoregulation model for the inverse design of indoor thermal environment. This investigation developed the CFD solver in OpenFOAM, the genetic algorithm by GenOpt, and the human body thermoregulation model in Matlab. A shell file was used to run those three parts in need automatically. The developed model was validated by the measured human skin temperature from literature. The model was further applied to design the thermal environments in an office with displacement ventilation for demonstration. In the office case with displacement ventilation, the thermal comfort was maximized when the air supply air temperature and velocity was 25 oC, and 0.08 m/s. Coupling thermoregulation model with CFD inverse design provides a more detailed way to optimize the indoor thermal environment, and at the same time, local thermal discomfort can be reduced.