Functional dyspepsia (FD) is a heterogeneous disorder associated with diverse pathophysiologic mechanisms. Studies have shown duodenal implications in the pathophysiology of FD. Duodenal hypersensitivity to acid, increased duodenal acid exposure, and abnormal responses to duodenal lipids or released cholecystokinin have been observed in patients with FD. Moreover, there is evidence indicating duodenal immune activation in FD. Alterations in the number of duodenal eosinophils or intraepithelial lymphocytes have been reported in a subset of FD patients, particularly in patients with post-infectious FD. Whether these abnormalities in the duodenum play a crucial role in the generation of dyspeptic symptoms needs to be elucidated. Further investigations on the relationship between duodenal abnormalities and well-known pathophysiologic mechanisms of FD are required. Furthermore, the causative factors related to the development of duodenal abnormalities in FD warrant further study.