The increase in the number of world's elderly population and changes in their lifestyle has triggered to the formation of diseases susceptible communities. Inherent with the aforementioned conditions, the need in andrographolide as one of natural remedies isolated from the leaves of Andrographis paniculata also increases. In this work, super-critical fluid extraction employing CO2-ethanol mixture as solvent has shown its capability in extracting andrographolide from dried leaves of A. paniculata. The andrographolide yield largely increased when the ethanol concentration in the solvent mixtures was increased from 0 to 12.5 mol %, but there was no significant increase in andrographolide yield as ethanol concentration was further increased. Although an enhancement of both temperature and pressure gave favorable effects on the yield of andrographolide, a crossover effect existed in this supercritical system causing no significant increase of andrographolide yield. The downflow mode performed the highest extraction efficiency compared to both upflow and horizontal-flow modes. Supercritical CO2-ethanol mixture containing 12.5 mol % ethanol flowed at 2 mL/min according to downflow mode at 323 K and 15 MPa was found to be the most effective in extracting andrographolide. The integral desorption model satisfactory described the extraction profile as shown by its low average error of about 5%.