Spray-dried aqueous extract from citrus by-product (“pastazzo”, ExO) was studied to evaluate the polyphenols content, the antioxidant properties and the inhibition of metalloproteinases over-expressed in dysmetabolic disease. During shelf life studies, ExO changes polyphenols content and decreases the antioxidant properties. Furthermore, Citrus flavonoids are unstable in gastric environment and ExO showed an incomplete in vitro dissolution rate in simulated biological fluids, probably due to their low solubility. For these reasons, formulation studies have been performed to develop spray-dried gastroresistant microsystems for oral administration. Our studies revealed that all the prepared gastroresistant microsystems preserved the polyphenols content, prolonged the shelf-life and the antioxidant efficiency of ExO and maintaining its inhibitory effects on metalloproteinases.