AbstractPepper oleoresin was extracted using supercritical fluid extraction (SCF) from Piper nigrum berries. The conditions for maximum extraction of piperine were arrived at by calculating the solubility parameters of piperine and carbon dioxide using the Hildebrandt solubility equation. The effect of entrainers such as methanol, ethanol, and acetone was evaluated using theoretical modeling. The results predicted therefrom were validated experimentally. SCF at 250 bar/50 °C/60 min gave maximum relative extraction of 61.7 and 87.61% of oleoresin and piperine, while addition of 30% (vol/wt) ethanol as co‐solvent enhanced the yield to 95.9 and 184.7% under similar conditions of SCF extraction as compared to ethanol extraction for 6 hr. The oleoresins obtained showed comparable antioxidant, anti‐inflammatory, and antimicrobial activities with their respective controls. Hence SCF extraction of pepper using ethanol as a co‐solvent promises a rapid and enhanced recovery of oleoresin and its constituents with a good bioactivity profile.Practical applicationsAlthough SCF is a promising alternative for extraction of spice oleoresins, high cost of operation limits the use of this technology. In this work, process intensification of SCF extraction of black pepper lead to one step extraction and purification, along with high yield of oleoresin and the principle component piperine, eventually decreasing the cost of production. Thus, the highly concentrated SCF extracted oleoresins can have better replacement value for whole spices and better distribution in food and pharmaceutical sector.