We report an efficient approach for fabricating organic/inorganic hybrid nanofibers for drugencapsulation and sustained release. In this study, a clay material, laponite (LAP), was first used toencapsulate amoxicillin (AMX) though ion exchange. The drug loaded LAP/AMX nanohybrid wassystematically characterized via different techniques. We show that LAP and AMX can be hybridized withan optimized loading percentage of about 10 ％ (w/w). Then, the LAP/AMX nanohybrid was incorporatedinto poly(lactic-co-glycolic acid) (PLGA) nanofibers though electrospinning to form a PLGA/LAP/AMXnanofibers based double-container drug delivery system (DDS). The fiber morphology was characterizedusing scanning electron microscopy (SEM). In vitro drug release behavior was examined using UV-Visspectroscopy. Finally, the antimicrobial activity of the PLGA/LAP/AMX nanofibers was investigatedagainst Staphylococcus aureus (S. Aureus) on solid medium. We show that the incorporation of LAP/AMXnanohybird did not significantly change the morphology of the PLGA nanofibers. The in vitro drug releasedata indicate that the PLGA/LAP/AMX nanofibers can avoid the burst release of AMX. Furtherantimicrobial activity and biocompatibility assays indicate that PLGA/LAP/AMX nanofibers shows nocompromise in antimicrobial activity relative to AMX powder and biocompatibility relative to PLGAnanofibers. We anticipate that this double-container DDS may find various applications in tissueengineering and pharmaceutical science.