Exposure to stressors can cause functional disorders and structural damage to the stomach. Sertraline (SER) is an antidepressant and curcumin (CUR) is a natural compound with many properties. The current study aimed to investigate the impacts of stress, SER, and CUR on the stomach tissue using stereological methods. In total, 24 male and 24 female Sprague-Dawley rats were divided into four groups. In the control group, the rats were not exposed to stress. However, the animals in stress, SER and, CUR groups were exposed to daily stress and were orally fed with distilled water, SER (10 mg/kg/day), and CUR (100 mg/kg/day), respectively. The volume, surface area, and number of nerve, parietal, and chief cells were evaluated by stereological methods. Results showed that stress increased the stomach and its mucosa and submucosa volumes, while it decreased the surface area of the mucosa. Furthermore, this disorder increased the number of neurons in the submucosa and myenteric plexuses while it decreased the number of parietal and chief cells. However, treating stressed rats with SER or CUR could prevent these changes. The results showed that the consumption of SER or CUR could be used as a preventive or adjunctive treatment for stressful situations.