Phenylketonuria (PKU) is a genetic enzyme defect affecting 1:10 000-20 000 newborn children every year. The amino acid phenylalanine (Phe) is not depleted but accumulates in tissues of several organs, which leads to severe medical conditions. A promising concept to restore the metabolism of the affected patients will be to orally administer the defective enzyme which will remove Phe in the intestine. Herein, capsosomes, a multicompartment carrier consisting of thousands of liposomes embedded within a polymeric carrier, are employed as encapsulation platform for this purpose. It is shown that the enzyme phenylalanine ammonia lyase can be entrapped within the liposomal compartments with preserved activity, demonstrated by the conversion of Phe into trans-cinnamic acid (t-ca). With the aim to mimic the dynamic environment in the intestine, the Phe conversion is performed in a microfluidic set up in the presence of human intestinal epithelial cells with applied intestinal flow and peristaltic motions. It is also shown that the microreactors are neither internalized by the cells nor exhibit inherent cytotoxicity while concurrently converting Phe into t-ca. Taken together, the first active extracellular multicompartment microreactor is reported using the relevant enzymes and settings toward the treatment of the medical condition PKU.