OBJECTIVEThis study aimed to evaluate the effect of bisabolol treatment on the activity and expression of the main enzymes of the glycolytic pathway in the submandibular and parotid salivary glands of Streptozotocin (STZ)-induced diabetic rats.DESIGNTwenty-four male Wistar rats, aged 60 days, were divided into four groups: Control, diabetic, control+Bisabolol, and diabetic+Bisabolol. A single intraperitoneal injection of Streptozotocin induced diabetes. The treated group received a daily dose of α-Bisabolol (25 mg/kg of body weight dissolved in 0.1 mL of sunflower oil) by gavage for 21 days. The untreated group received only the vehicle. All animals were euthanized 28 days after induction, and the parotid and submandibular glands were removed, frozen in liquid nitrogen, and stored at -80 °C. The expression of the main enzymes of the glycolytic pathway was analyzed through RT-qPCR. Biochemical analyses were conducted to verify Hexokinase (HK), Phosphofructokinase (PFK), Pyruvate kinase (PK), and Lactate dehydrogenase (LDH) activity. The data were statistically compared via the Student t-test and analysis of variance (ANOVA) followed by Tukey's test, where results were considered statistically significant at p < 0.05.RESULTSIn general, bisabolol restored the HK and PFK activities and also restored Hexokinase 2 (Hk2), Phosphofructokinase muscle isoform (Pfkm) and Phosphofructokinase platelet isoform (Pfkp) expression in the bisabolol-treated diabetic rats. The LDH activity increased in diabetic rats with bisabolol.CONCLUSIONBisabolol treatment restored the activity and expression of key glycolytic enzymes, suggesting that it may have therapeutic potential in mitigating the salivary glands metabolic dysregulation caused by diabetes in rats.