Derivatives of (+/-)-ethyl mandelate are important intermediates in the synthesis of numerous pharmaceuticals. Therefore, efficient routes for the production of these derivatives are highly desirable. The short-chain dehydrogenase/reductase (SDR) is a biocatalyst that could potentially be applied to the synthesis of (+/-)-ethyl mandelate; however, this enzyme requires the reduced form of the cofactor nicotine adenine dinucleotide (phosphate) (NAD(P)H), which is expensive. In this study, we developed a co-immobilization strategy to overcome the issue of NADPH demand in the SDR catalytic process. The SDR from Thermus thermophilus HB8 and the NAD(P)-dependent glucose dehydrogenase (GDH) from Thermoplasma acidophilum DSM 1728 were co-immobilized on silica gel. The properties and the catalytic abilities of this dual-enzyme system were evaluated. A final yield of 1.17mM (+/-)-ethyl mandelate was obtained from the catalytic conversion of ethyl benzoylformate, with a conversion rate of ethyl benzoylformate to (S)-(+)-mandelate of 71.86% and in an enantiomeric excess of >99% after 1.5h. This system offers an efficient route for the biosynthesis of (+/-)-ethyl mandelate.Graphical Abstract p id=Par2In this study, we developed a co-immobilization strategy to overcome the issue of NADPH demand in the SDR catalytic process. The SDR from Thermus thermophilus HB8 and the NAD(P)-dependent glucose dehydrogenase (GDH) from Thermoplasma acidophilum DSM 1728 were co-immobilized on silica gel. Results showed that, this dual-system offers an efficient route for the biosynthesis of (+/-)-ethyl mandelate. [GRAPHICS] .