This research paper explains the nature of pharmacogenetics and anti-diabatic roles of Azadirachta indica (neem) leaves. Pharmacogenetic serials of phytochemical checks (microscopy, physicochemical tests ash test; extractive values) were performed on the shade-dried leaves. Extracts were made methanolically and extraction was done using water. The methods used in test were antioxidant (DPPH, ABTS), inhibition of α-amylase, inhibition of α-glucosidase and in vitro experiments. The in vivo anti-diabetic efficiency was studied on the high-fat diet/ streptozotocin (HFD/STZ) induced Type 2 diabetic rat by administration of 100, 200, and 400 mg/kg of 30 days. Blood gligatorid levels, glucose intolerance, lipid peroxidation, and antioxidant status and histopathology of pancreatic tissues were assessed and metformin was performed as a positive control. HPLC/HPTLC demonstrated rutin, quercetin and ellagic acid using methanolic extract. Extrates showed good ability of antioxidant and enzyme inhibition; the 400 mg/kg dose notably corrected glycemia, reversed lipid and antioxidants levels. The histology revealed the recovery of pancreatic structure.