The aim of the current research was to determine the effects of cornelian cherry (Cornus mas L.) stone in Zucker diabetic fatty (ZDF) rats and characterize antioxidant profile (antioxidant activity, total polyphenol, phenolic acids and flavonoids) in cornelian cherry stone. A total of 24 male ZDF rats were divided into three groups: lean (non-diabetic), control (diabetic) and E (experimental group treated with dose 250 mg/kg body weight of cornelian cherry stone). The blood glucose levels in E group (9.83 ± 1.5 mmol/L) were significantly lower (P < 0.001) compared to the control (18.83 ± 2.56 mmol/L) in the end of the experiment. The antioxidant activity tested by DPPH method in cornelian cherry stone showed 7.84 mg TEAC/g (TEAC – trolox equivalent antioxidant activity). The content of total polyphenols was 29.61 mg GAE/g(GAE – gallic acid equivalent), from which flavonoids represented 1.56 mg QE/g(QE – quercetin equivalent) and phenolic acids 6.66 mg CAE/g(CAE – caffeic acid equivalent). The obtained results confirmed that cornelian cherry stone is a good source of antioxidant compounds and is able to positively participate in the glucose regulation in ZDF rats.