Nowadays, combination drugs shows increasing advantageous merit in treating complex disease than single target drug, but rapid discovery of combinatorial bioactive components as drug candidates is a much greater challenge. In this work, a metabolic distribution-oriented network regulation strategy was developed for the identification of effective combination. The extract of Ginkgo biloba (EGB) was taken as a case study. Firstly, comprehensive chemical profiling and metabolic exposure of EGB in a pathological state were conducted. Then the effective combination was screened by combining network regulation and the metabolic exposure level of EGB. Finally, a combination of 12 active compounds was found for treatment of ischemia stroke, showing bioactivity equivalence with original EGB. The results also indicated that beside the well-known ginkgolides and flavonoids, trace compounds might also play an important role of the holistic effect of EGB.