In recent years, there have been growing efforts to understand and modulate stigma and prejudice from the standpoint of the psychological flexibility model, a pragmatic model of complex human behavior. The present paper provides an overview of the empirical evidence on the applicability of the psychological flexibility model, and its applied strategy, acceptance and commitment therapy (ACT), to stigma and prejudice. Preliminary findings suggest that the psychological flexibility model and ACT are promising avenues for reducing stigma and prejudice; however, further investigation and refinement of the model and ACT are crucial for significantly ameliorating human suffering related to stigma and prejudice.