The present study intended to examine the effect of bergapten and possible mechanisms involved in the treatment of migraine-associated symptoms in the rat model. Five doses of nitroglycerin (10 mg/kg) were injected intraperitoneal to induce migraine headaches in rats with a one-day break between each dose. Treatment groups received nitroglycerin followed after 1 day by bergapten (50 or 100 mg/kg), saline (10 mL/kg), or sumatriptan (50 mg/kg) once daily for 10 days. Behavioral observations were analyzed 2 h after nitroglycerin injections and 1 h 40 min after treatment. The animals were sacrificed 24 h after the last treatment dose. Samples of trigeminal nucleus caudalis (TNC) and cerebral cortex were collected and analyzed for antioxidant activity and expression of inflammatory markers by immunohistochemistry and enzyme-linked immunosorbent assay. Our findings revealed that bergapten notably decreases headache by altering mechanical allodynia, thermal allodynia, light phobicity, and the number of head-scratching incidence in rats. In the cortex and TNC regions, antioxidant factors were restored, and lipid peroxidation was significantly reduced. Furthermore, bergapten decreased the expression of inflammatory markers, such as nuclear factor kappa B (NF-Kb) and tumor necrosis factor-alpha (TNF-α), as evidenced by immunohistochemistry and ELISA. These results suggest that bergapten exhibits headache-relieving activity, possibly mediated through antioxidant and anti-inflammatory pathways.