Purpose: In this study, we aimed to investigate the effects of β-caryophyllene against oxidative stress-induced apoptosis in the animal model of diabetes. Materials and Methods: Experimental diabetes was induced in the rat model through the administration of streptozotocin. Plasma samples were tested for the lipid profile. Plasma insulin levels were measured by performing electrochemical immunoassay. Fasting blood glucose was measured using the glucometer. Intracellular levels of reactive oxygen species (ROS) were measured through dichlorodihydrofluorescein diacetate method. Markers of oxidative stress such as catalase (CAT), reduced glutathione (GSX), malondialdehyde (MDA), and superoxide dismutase (SOD) levels were determined by using the colorimetric kits. Expression of apoptotic proteins such as Bax, Bcl-2, Pro-caspase 9, caspase 9, and β-actin was analyzed using the Western blot technique. Results: According to our results, β-caryophyllene normalized the body weight of diabetic rats and improved the lipid profile of the experimental animals. It also normalized the levels of fasting blood glucose. Moreover, the plasma insulin levels significantly increased after the administration of β-caryophyllene. The β-caryophyllene treatment caused a significant decline in the ROS and MDA levels together with an increase in the levels of CAT, SOD, and GSX levels in diabetic rats. Interestingly, the markers of apoptosis such as Bax and caspase 9 decreased after the administration of β-caryophyllene in the neural tissue of diabetic rats. However, the levels of Bcl-2 protein were increased in the β-caryophyllene-treated rats. Conclusion: β-Caryophyllene exhibits significant antidiabetic effect, which might be due to its capacity to reduce oxidative stress and inhibit apoptotic markers in the peripheral neural tissue of diabetic rat. These results point toward the potential of β-caryophyllene in the treatment of diabetes.