Diabetes mellitus is a very complicated and long-term disease. Diabetic patients are always at risk of creating more complicated diseases in a very short time, as the damage of body organs is very fast if the situation becomes serious and untreated properly. Until yet there is no such medicine that could properly or completely treat diabetes mellitus. So there is an urgent need for advanced computational methods to identify novel therapeutics in a short time and at cheap rates. In this chapter, we have explained the status of diabetes mellitus, publications records, cases studies, mathematical models, and the importance of computer-aided aided design and its application in network pharmacology for the medicinal research of diabetes mellitus, also highlighted different medicine and potential targets for promoting antidiabetic drug research. More detailed studies of diabetic patients’ data set are required using advanced computational power to facilitate and speed up the antidiabetic drug research.