In treating type 2 diabetes, avoiding glucose reabsorption (glucotoxicity) and managing hyperglycemia are also important. A metabolic condition known as diabetes (type-2) is characterized by high blood sugar levels in comparison to normal Bilosomes (BLs) containing Dapagliflozin (Dapa) were formulated, optimized, and tested for oral therapeutic efficacy in the current investigation. Used the Box Behnken design to optimize the Dapa-BLs, formulated via a thin-film hydration technique. Bile salts (X1) concentration, edge activator (X2) in mg, and non-ionic surfactant (X3) were the independent variables. The Entrapment Efficiency (Y1), Particle size (PS), polydispersity index (PDI), and zeta potential (ZP), were selected as dependent variables. To get the optimal formula, use Design-Expert® software for numerical optimization. The optimal bilosomal formula was selected by boosting %EE, ZP (absolute value), and in vitro drug release while also considering decreasing PS and PDI. Ex vivo skin permeation, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were evaluate the optimized formulation. The in vivo pharmacodynamics activities of the optimized formula were examined on rats and compared to that of the oral Dapa solution. The optimized Dapa-BLs were shown a particle size of 155.36±2.48 nm and an entrapment efficiency of 86.37±2.6%. The SEM image showed a spherical particle with sharp boundaries. The drug release study revealed a significant enhancement in Dapa release (75.31 ± 2.68%) from Dapa -BLs as compared to drug solution (30.46 ± 3.64%). The results of the exvivo permeation and pharmacokinetic studies revealed a 4.49 times higher flux and 3.41 folds higher AUC_0-t than drug solution. The antidiabetic activity results showed significant (P < 0.05) enhancement in therapeutic efficacy than drug solution. The results also showed marked improvement in biochemical parameters. Our findings suggested, the prepared Dapa loaded bilosomes was found to be an efficient delivery in the therapeutic efficacy in diabetes.