Biocatalytic asymmetric sulfoxidation represents a green method to prepare the useful and valuable enantiopure sulfoxides, but this method sometimes suffers from unsatisfied enantioselectivity and low productivity due to substrate and product inhibitions. Here we developed an aqueous/ionic liquid (IL) biphasic system for simultaneously enhancing the enantioselectivity and productivity of P450 monooxygenase-catalyzed asymmetric sulfoxidations of sulfides 1, 3, 5, 7, and 9, as the first example of this kind for a biooxidation. Escherichia coli (P450pyrI83H-GDH) coexpressing P450pyrI83H monooxygenase and glucose dehydrogenase was engineered for the asymmetric sulfoxidations with cofactor recycling, giving higher R-enantioselectivity than any other known P450 monooxygenases and showing high specific activities. The inhibition to the reactions and the toxicity to the cells of the substrates and products were investigated and mostly avoided by using a KP buffer/[P 6,6,6,14 ][NTf 2 ] biphasic reaction system, in which the IL showed excellent biocompatibility to the cells and high solubility to the substrates and products. Sulfoxidations of 1, 3, 5, 7, and 9 with the resting E. coli cells in the biphasic system increased the product concentration from 9.4 to 20 mM for (R)-phenyl methyl sulfoxide 2, from 1.9 to 9.9 mM for (R)-4-fluorophenyl methyl sulfoxide 4, from 5.4 to 16 mM for (R)-ethyl phenyl sulfoxide 6, from 4.2 to 22 mM for (R)-methyl p-tolyl sulfoxide 8, and from 5.7 to 24 mM for (R)-methyl pmethoxyphenyl sulfoxide 10, respectively, and improved the product ee from 85 to 99% for (R)-2, from 80 to 98% for (R)-4, from 88 to 96% for (R)-6, from 35 to 62% for (R)-8, and from 53 to 67% for (R)-10, respectively. The enhancements in enantioselectivity are possibly caused by the low substrate concentrations in the aqueous phase of the biphasic system. Preparative sulfoxidations to produce the useful and valuable sulfoxides (R)-2, (R)-4, and (R)-6 in 99%, 98%, and 96% ee, respectively, were demonstrated.