Empagliflozin (EMP) is an oral antihyperglycemic agent for type 2 diabetic patients. The molecular binding of EMP to bovine serum albumin (BSA) was elucidated by a combined experimental/computational approach to fulfill the pharmacokinetics and pharmacodynamics gaps of the cited drug for further development. Fluorescence, synchronous, and three‐dimensional fluorescence spectroscopy verified that EMP quenched BSA native fluorescence through a dual static/dynamic mechanism, that was further supported by Fӧrster resonance energy transfer and UV absorption spectroscopy. Fourier transform infrared spectroscopy revealed the conformational variations in BSA secondary structure induced by EMP. Thermodynamic properties of the BSA‐EMP complex were also investigated, and the hydrophobic interactions’ role in the binding process was demonstrated by the computed enthalpy (ΔH= 6.558 KJ mol^‐1