Ginsenoside 20-O-β-D glucopyranosyl-20(S)-protopanaxadiol (compound K), a minor ginsenoside, is not found in white raw ginseng, but has better bioavailability than the major ginsenosides in ginseng. Employing commercial enzyme packages for industrial applications, the optimum conditions for enzymatic transformation for the highest content of compound K was explored to enhance the health benefits of ginseng extract. Cytolase PCL 5 was selected from commercial enzyme packages nominated for high β-glucosidase activity. By response surface methodology, the optimal conditions were identified as 78 h of treatment at pH 4.3 at 55.4 °C for 2.068 mg/mL of compound K, showing good agreement with the experimental value.