Glucokinase plays a critical role in glucose homeostasis and the mutations in Glucokinase gene results in altered catalysis of the enzyme leading to type 2 diabetic condition. The catalysis takes place by super open and closed conformations of enzyme which will be disturbed by the mutations. The in silico mutagenic studies reveal several mysterious points about the impact of mutations on the structural and functional behaviour of glucokinase that are in best correlation with its enzyme activities. This study provides an insight into the understanding of the clear possible reasons for the altered activities of glucokinase under mutated condition and the probable consequences with respect to the pathogenesis of diabetes. This problem can be solved by the usage of glucokinase activators that have the ability to bind with the allosteric site of glucokinase and increase its activity by specific folds. Structure based drug design helps to develop more efficient lead molecules based on the structural information of the glucokinase. These molecules can be used to for the treatment and management of type 2 diabetes.