Obesity and associated metabolic disorders became the global issue. Various treatment strategies have been employed for the comfort and recovery of the diseased condition. Patients suffering with obesity are many times found to be diabetic. Diacylglycerol o-acyl transferase inhibitor (DGATi/ DGAT inhibitor) is found to be most effective treatment in management of diabetes mellitus, obesity and hyperlipidemia as well. Obesity causes the accumulation of triglycerides (TGs) in adipose tissue. The enzyme pancreatic lipase hydrolyzes the triglyceride to monoacylglycerol and fatty acids. DGAT is involved in catalysis of the very last step of triglyceride synthesis. DGAT-I is present in adipose tissue, liver and small intestine. DGAT-I plays a vital role in the absorption of lipid, also in accumulation of fat cells in the liver. Animal studies indicated that inhibition of this DGAT-I enzyme is a promising target for the treatment and management of obesity and diabetes mellitus and related metabolic disorders. The physicochemical properties, pharmacokinetics, drug-likeliness, lead likeliness, synthetic accessibility of the newly designed ligands was investigated through computational screening. Biological activity was predicted using Molinspiration. The anti-diabetic potential of these ligands was predicted with PASS online (Prediction of Activity Spectra for Substances), and about 36 molecules were investigated through this process. The results obtained from this research work may be utilized for the development of new anti-diabetic, anti-obesity, anti-cancer drugs. Further these molecules must be explored to higher computational studies at molecular and cellular levels. In-vivo and in-vitro studies can also be performed to forecast the promising treatment strategy for diabetes mellitus and obesity