Type 2 diabetes mellitus (T2DM) is a complex disease with multiple pathophysiological defects and generally requires a combination of antidiabetic agents to achieve glycemic targets. In this context, a fixed-dose combination (FDC) of dipeptidyl peptidase-4 inhibitors vildagliptin sustained-release (SR) and a sodium-glucose cotransporter type 2 inhibitors dapagliflozin appear to be an attractive approach. There is a strong rationale for combining vildagliptin with dapagliflozin. They have complementary mechanisms of action that address several pathological pathways and are effective at all disease stages. Vildagliptin and dapagliflozin are generally well tolerated, with low hypoglycemia risk. Moreover, they exert beneficial pleiotropic actions on the cardiovascular system and kidneys, lower body weight, and blood pressure and reduce pill burden, providing an important option for managing a broad patient population. For Indian T2DM patients, who have a high prevalence of cardiometabolic risk factors, this combination would be an appropriate choice. Furthermore, the once-daily 100 mg SR dosage of vildagliptin meets the requirements for compliance and adherence. However, data on the vildagliptin SR and dapagliflozin FDC are limited. This review summarizes the available evidence and provides rational, practical guidance for the optimal clinical use of vildagliptin SR and dapagliflozin FDCs in T2DM patients.