Polymeric particles are a versatile class of local or systemic drug delivery systems, used to improve drugs pharmacokinetics and pharmacodynamics along with patient compliance. Herein, we report a rapid, scalable, and optimized method to encapsulate ciprofloxacin (CPx), a poor water soluble antimicrobial agent, in gelatin microparticles by single step processing via spray-drying of an aqueous solution. The developed particles show mainly a wrinkle morphology with a unimodal distribution, with mean diameters ranging between 2 and 4 μm, depending on the processing conditions. The encapsulation of 1, 2 and 5 wt% CPx narrows the size distribution (1–3 μm). In vitro release experiments showed that up to 80% of encapsulated drug is released during the first 6 h, and the release kinetics was best fitted with the Korsmeyer-Peppas model, explained by the superimposition of drug diffusion and polymer chain relaxation. The minimal inhibitory concentrations against S. aureus and E. coli, obtained from pure and encapsulated ciprofloxacin, demonstrated that the spray-drying process does not inhibit the drug's bioactivity or the process feasibility. Thus, spray-drying of protein-drug particle systems is an advantageous method to produce microparticles with potential to lung delivery systems.