Supercritical fluid extraction was used to extract the alkaloid N-[7-(3′,4′-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl]pyrrolidine from leaves of Piper amalago L. A three-level orthogonal array design matrix, OAD OA9(34), was used for optimization of the parameters of supercritical extraction of the alkaloid, employing supercritical carbon dioxide: extraction time (20, 40, and 60 min), temperature (40, 50, and 60°C), pressure (150, 200, and 250 bar), and the use of cosolvents (ethanol, methanol, and propyleneglycol). All parameters had significant effect on the alkaloid yield. The alkaloid yield after 60 min of extraction without cosolvents at 9 different conditions (32) in terms of temperature (40, 50, and 60°C) and pressure (150, 200, and 250 bar) was also evaluated. The optimal yield (≈3.8 mg g−1) was obtained with supercritical CO2 + methanol (5% v : v) at 40°C and 200 bar for 60 min of extraction.