OBJECTIVE The current investigation aimed to assess the antioxidant, antidiabetic and antilipidemic effects of the aqueous extract of aerial part of Cotula cinerea (C. cinerea). BACKGROUND Cotula cinerea (Del). which belongs to the Asteraceae family is commonly used traditionally for the treatment of diabetes. OBJECTIVE The objective of the study was to study the effect of the aqueous C. cinerea extract on glucose and lipid metabolism in normal and streptozotocin-induced diabetic rats using a single and repeated oral administration. METHODS A preliminary phytochemical screening and the quantification of phenolic and flavonoid contents as well as the antioxidant activity using three methods (DPPH, FRAP and ABTS) were carried out. The effect of a single and repeated (15 days of treatment) oral administration of the aqueous extract of aerial part of Cotula cinerea (AEAPCC) at a dose of 20 mg/kg on glucose and lipid profile was examined in normal and streptozotocin-induced diabetic rats. Additionally, histopathological examination of the pancreas and liver was carried out according to the Hematoxylin-Eosin method. RESULTS AEAPCC (20 mg/kg) showed a significant blood glucose-lowering activity in both normal and diabetic rats after a single and repeated oral administration during 15 days. The aqueous extract was also able to decrease the plasma triglycerides levels in both normal and diabetic rats after 15 days of oral treatment at a dose of 20 mg/Kg while no effect was observed on plasma cholesterol levels. In addition, the results show that AEAPCC exhibits an in vitro antioxidant activity using different tests. Histopathological analysis of the pancreas and liver of AEAPCC-treated diabetic rats has revealed that AEAPCC had a beneficial effect on the architecture of these organs while no improvement of glucose tolerance was noticed using the glucose tolerance test. Furthermore, the results showed that the extract is rich in several phytochemical compounds and exhibited an important antioxidant activity. The phytochemical screening revealed that AEAPCC contains polyphenolic compounds, flavonoids, tannins, alkaloids, saponins, quinones, sterols, terpenoids, anthroquinones and reducing sugars. Whereas, it is free from glycosides. CONCLUSIONS In conclusion, this study demonstrates that Cotula cinerea possesses a beneficial effect on diabetes. Further investigations are required to study the mechanism of action of the antidiabetic effect of this plant.