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Diabetes mellitus is a heterogeneous group of metabolic dysregulation that shares phenotype of hyperglycemia and for which genetic and environmental risk factors act synergistically. Dietary acid load and low pH of interstitial fluid are the most important, factors reducing insulin sensitivity and making the body condition worse in Type 2 diabetes mellitus (T2DM). Several pharmacological classes of oral antidiabetic drugs (OADs) are actually reachable for the treatment of T2DM. These drugs are designed especially to reduce blood glucose level but not necessary to improve insulin resistance. This latter with OADs side effects may affect the whole therapeutic strategies of T2DM. The kind of diet can deeply affect the organism by the generation of acid or base precursors. Indeed, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, while fruit and vegetables are alkalizing. However, milk, fats and sugars are considered neutral, which have an insignificant effect on acid-base balance. To save cell function, the pH of body fluids is maintained constant by various systems which became impaired with increase in age and many pathological situations. This review proposes to highlight the effect of dietary acid load on the pathogenesis and management of T2DM as well as on its influence on the heterogeneity of OADs responses observed in diabetic patients. [ABSTRACT FROM AUTHOR]