Diabetes mellitus (DM) is a group of metabolic disorders with one common manifestation: elevated blood sugar or hyperglycemia. The diagnosis of diabetes is the most crucial point due to chronic hyperglycemia. This chapter improves the performance of the Classification and Regression Trees (CART) algorithm because the accurate classification of diabetes depends on the algorithm efficiency. Authors use the accuracy rate for the objective function in the prediction process by Genetic Algorithm (GA). The proposed GA-CART algorithm provides the best performance at 96.05%.