A process of preparation of an antimicrobial powder coating composition comprising the steps: a) transforming a natural antimicrobial agent into a salt-form and micronizing the resulting antimicrobial salt into powder, b) mixing at least one of the natural antimicrobial salt together with at least one amino-reactive thermoplastic binder resin, c) subjecting the mixture to a melt compounding process at a temperature in a range of 80 to 230.degree. C., at a residence time period in a range of 5 to 60 seconds, using at least one co-rotating twin-screw extruder with a soft screw design having conveying elements offering a high D/d ratio and having mixing forward kneading block elements, d) cooling the extrudate, and e) micronizing into powder particles. The process forms a powder coating composition containing a natural antimicrobial agent which results in high quality antimicrobial coatings showing a homogeneous distribution of the antimicrobial agent in the coating and a stable antimicrobial activity.