Background: Sodium benzoate is a widely used food preservative permitted in Ukraine with an acceptable daily intake of 5 mg/kg body weight. However, exposure to elevated doses may induce oxidative imbalance and metabolic disturbances. Therefore, the search for effective protective agents against sodium benzoate–induced oxidative stress remains relevant. Resveratrol is a natural polyphenolic compound known for its antioxidant, anti-inflammatory, and cytoprotective properties. Objective: To evaluate the effect of resveratrol on free radical processes and antioxidant defense parameters in rats exposed to elevated doses of sodium benzoate. Material and Methods: The study was conducted on 42 adult male rats. Sodium benzoate was administered intragastrically at a dose of 30 mg/kg body weight daily for 28 days. Resveratrol was administered intragastrically at a dose of 20 mg/kg body weight. Animals were euthanized on days 14, 21, and 28. Oxidative stress and antioxidant status were assessed by measuring thiobarbituric acid reactive substances (TBARS), products of oxidative modification of proteins, ceruloplasmin content, reduced glutathione levels, and catalase activity in blood serum and liver tissue. Results: Sodium benzoate exposure resulted in a significant increase in lipid peroxidation and protein oxidative modification, accompanied by a decrease in reduced glutathione levels and catalase activity in both blood serum and liver tissue. By the end of the experiment, TBARS levels increased 5.1-fold in serum and 3.7-fold in liver tissue compared to controls. Resveratrol administration significantly attenuated oxidative damage, restored reduced glutathione levels to near-control values, and increased catalase activity throughout the experimental period (p ≤ 0.05). Conclusions: Resveratrol effectively reduces sodium benzoate–induced oxidative stress and restores antioxidant defense mechanisms in rats, indicating its potential protective role against preservative-associated oxidative damage.