Luffa acutangula is a species of Luffa. It is also known as the ridge gourd, angled gourd. Previous proven activities based on literature review show that some plant parts have anti-diabetic properties, The ability of plant aerial parts to prevent diabetes, however, has not been proved scientifically. The current study's objective was to evaluate the anti-hyperglycemic efficacy of an ethanolic extract of Luffa acutangula aerial parts (EELA) in type II diabetic rats that had been induced by streptozotocin and nicotinamide. After 15 minutes of NIC (120 mg/kg i.p.) treatment, type 2 diabetes was established by administering STZ (60 mg/kg, i.p.). Diabetic rats received EELA (400 and 800 mg/kg, p.o., respectively) for 28 days. Blood glucose, SGPT, SGOT, blood urea, creatinine, haemoglobin, total cholesterol, triglycerides, LPO, and GPX levels were all considerably reduced in diabetic rats who received EELA treatment. Nevertheless, EELA-treated diabetic rats exhibited body weight, HbA1c, CAT, SOD, GSH, hexokinase, liver glycogen, and G6P that were considerably greater. Histopathological studies have demonstrated that treatment groups experienced pancreatic beta cell regeneration. By using GC-MS analysis, it is proven that EELA contains Phenol, Phytol, Maleic anhydride, Neophytadiene, Furan, Lutein, and Eugenol. According to the results of the current investigation, EELA may be effective in treating Diabetes mellitus without producing any overt harmful effects. The anti-diabetic effects of EELA were comparable to those of the common medication Glibenclamide. The laboratory results from this investigation support the conventional usage of EELA to treat diabetes, indicating a need to isolate and assess active ingredients responsible for the demonstrated biological activity for the upcoming studies.