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Hodgsonia heteroclita has been known as an important traditionally consumed medicinal plant of North-East India known to have antidiabetic properties. This study aims to investigate the effects of the ethanolic fruit extract of Hodgsonia heteroclita against hyperglycemia and hyperlipidemia by using streptozotocin (STZ) treated diabetic mice. The fruits of H. heteroclita were collected from the various parts of Kokrajhar district, Assam India (Geographic coordinates: 26°24′3.85″ N 90°16′22.30″ E). Basic morphological evaluations were carried out by the Botanical Survey of India, Eastern circle, Shillong, who also certified and identified the plant. Hexane, chloroform, and ethanolic extracts of the fruit of H. heteroclita were investigated for α-amylase inhibition assay as a rapid screening tool for examining anti-diabetic activity. The efficacy of ethanolic extract at a dose of 100, 200, and 300 mg/kg body weight was tested for 21 days in STZ-induced diabetic mice. The body weight, fasting plasma glucose and serum lipids, and hepatic glycogen levels were measured in experimental animals to examine the antihyperglycemic and antihyperlipidemic efficacy of the extract. Both HPTLC and LC-MS analysis was performed to examine the phyotochemicals present in the ethanolic extract of H. heteroclita. It has been observed that treatment with the ethanolic extract dose-dependently reduced the plasma glucose levels, total cholesterol, low density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, triglyceride, and increased the body weight, liver glycogens and high-density lipoprotein-cholesterol in STZ treated diabetic mice. HPTLC demonstrated the presence of triterpene compounds and LC-MS analysis revealed the presence Cucurbitacin I, Cucurbitacin E, and Kuguacin G as the triterpene phytoconstituents. The present study demonstrated that ethanolic fruit extract of H. heteroclita improved both glycemic and lipid parameters in mice model of diabetes. Graphical abstract depicting the beneficial role of Hodgsonia heteroclita in the regulation of anti-hyperglycemic and anti - hyperlipidemic activities. [Display omitted] • Diabetes is a chromic metabolic disorders affecting worldwide population. • Hodgsonia heteroclita is a traditionally consumed medicinal plant of North-East India with antidiabetic properties. • Ethanolic fruit extract of H. heteroclita improved glycemic and lipid profiles in diabetic mice. • H. heteroclita can be used for the development of effective new medications for diabetes. [ABSTRACT FROM AUTHOR]