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The drug-loaded self-double-emulsifying drug delivery system (SDEDDS) was prepared, and its preliminary pharmacodynamics was investigated.The type and concentration of oil phase,inner aqueous phase and emulsifier were screened to prepare drug-loaded SDEDDS.Next, the optimum formulations were characterized based on microstructure, volume-weighted mean droplet size, self-emulsifying rate, yield, storage stability, in vitro release and in vivo pharmacodynamics was studied.It was showed that SDEDDS could successfully serf-emulsify into water/oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect protein activity in gastric environment.Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.