Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a promising palliative option for patients with refractory epilepsy. However, crucial questions remain unanswered: Which patients are the optimal candidates? How, where, and when to stimulate the STN? And what is the mechanism of STN-DBS action on epilepsy? Thus, we reviewed the clinical evidence on the antiepileptic effects of STN-DBS and its possible mechanisms on drug-resistant epilepsy, its safety, and the factors influencing stimulation outcomes. This information may guide clinical decision-making. In addition, based on the current knowledge on the effect of STN-DBS on epilepsy, we suggest research that needs to be carried out in the future.