© 2021 Walter de Gruyter GmbH, Berlin/Boston.Olive (Olea europaea L.) plays a promising role in pharmaceutical, nutraceutical, and cosmetic production. On the other hand, olive leaf is widely used in folk medicine due to its antihyperglycemic activity. For this aim, possible effects of olive leaf extract (OLE) in the brain tissue of streptozotocin-induced diabetic rats were investigated. A total of 28 male rats were divided into four equal groups as control, diabetic (single dose of 45 mg/kg streptozotocin, i.p.), OLE (500 mg/kg/day), and diabetic + OLE groups. The study was terminated 21 days after the diabetes model was formed. At the end of the study, all the animals were sacrificed and blood and brain tissues were isolated. Relative brain weights, complete blood count, blood glycated hemoglobin, serum glucose, total protein, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, insulin, gonadal hormone levels, production and messenger ribonucleic acid (mRNA) levels of proinflammatory cytokines and mediators, total thiol, total oxidative stress, and total antioxidant status levels and fatty acid composition in brain tissue were measured in all study groups. In diabetic rats, relative brain weight and serum insulin level decreased, glycated hemoglobin, oxidative stress, production and mRNA level of proinflammatory cytokines and mediators increased, hyperglycemia, hypercholesterolemia and hypertriglyceridemia, degraded fatty acid composition, anemia, leukopenia, and thrombocytopenia occurred. After OLE treatment, a remarkable improvement in most of these parameters, except gonadal hormones, has been observed in diabetic rats. This study suggests that olive leaf can be a precious neuroprotective agent in diabetes.