Electro-hydrodynamic processing, comprising electrospraying and electrospinning techniques, has emerged as a versatile technology to produce nanostructured fiber-based and particle-based materials. In this work, an antimicrobial active multilayer system comprising a commercial polyhydroxyalkanoate substrate (PHA) and an electrospun PHA coating containing in situ-stabilized silver nanoparticles (AgNPs) was successfully developed and characterized in terms of morphology, thermal, mechanical, and barrier properties. The obtained materials reduced the bacterial population of Salmonella enterica below the detection limits at very low silver loading of 0.002 ± 0.0005 wt %. As a result, this study provides an innovative route to generate fully renewable and biodegradable materials that could prevent microbial outbreaks in food packages and food contact surfaces.