The rare ginsenoside F2 and Compound K (CK) have high pharmacological activities in the treatment and prevention of diseases, but are difficult to obtain in nature. In this study, the extracellular enzymes from Aspergillus niger Wu-16 are applied to produce ginsenoside F2 and CK. The results show that the enzymes could catalyze the conversion of the substrate Rb1 to ginsenoside F2 and CK. The conversion conditions were optimized with a reaction time of 48 h, pH = 3, temperature of 55 °C, and enzyme-to-substrate ratio of 0.8. After the response surface optimization, the maximum conversion rates of ginsenoside F2 and CK were 50.11 % and 33.50 % respectively. On this basis, the highest conversion rate of rare ginsenoside CK reached 56.10 % by adding Co2+ with concentrations of 0.5 mM. This study provided a certain reference value for the production of rare ginsenosides F2 and CK with the advantage of enzymes catalysis.