OBJECTIVE: This study aimed to evaluate the antidiabetic efficacy of microemulsions formulated with cardamom oil, black seed oil, and olive oil. The goal was to determine the optimal formulation for stable microemulsions and assess their potential as innovative drug delivery systems for the antidiabetic drug repaglinide. METHODS: Initial phase diagrams were constructed to identify the optimal ratios of oil, water, surfactant (Tween 80), and cosurfactant (ethanol) for producing stable microemulsions. The physical attributes of the resulting formulations, such as droplet size, zeta potential, and morphology, were characterized using transmission electron microscopy. Drug release profiles of microemulsions containing repaglinide were evaluated using the dialysis method. Moreover, vivo studies were conducted to assess the therapeutic efficacy of cardamom oil microemulsions compared to standard commercial repaglinide formulations. RESULTS: Microemulsions exhibited suitable properties with optimal particle size, well-defined spherical droplets, and optimized zeta potential. Drug release studies indicated that cardamom oil-based microemulsions demonstrated superior release characteristics, providing a more sustained and controlled release of repaglinide compared to microemulsions containing black seed or olive oil. In vivo studies revealed a significant improvement in antidiabetic outcomes with cardamom oil microemulsions over standard commercial repaglinide formulations. The enhanced efficacy was attributed to improved bioavailability and the controlled release properties of the drug. CONCLUSION: This research underscores the potential of cardamom oil-based microemulsions as effective antidiabetic drug delivery systems. With superior physicochemical properties and controlled release profiles, they promise innovative treatment options for diabetes, potentially improving therapeutic outcomes for patients.