AbstractPlastic pollution is one of the main worldwide environmental concerns. Our lifestyle involves persistent plastic consumption, aggravating the low efficiency of wastewater treatment plants in its removal. Nano/microplastics are accumulated in living beings, pushing to identify new water remediation strategies to avoid their harmful effects. Enzymes (e. g., Candida rugosa‐CrL) are known natural plastic degraders as catalysts in depolymerization reactions. However, their practical use is limited by their stability, recyclability, and economical concerns. Here, enzyme immobilization in metal‐organic frameworks (CrL_MOFs) is originally presented as a new plastic degradation approach to achieve a boosted plastic decomposition in aqueous systems while allowing the catalyst cyclability. Bis‐(hydroxyethyl)terephthalate (BHET) was selected as model substrate for decontamination experiments for being the main polyethylene terephthalate (PET) degradation product. Once in contaminated water, CrL_MOFs can eliminate BHET (37 %, 24 h), following two complementary mechanisms: enzymatic degradation (CrL action) and byproducts adsorption (MOF effect). As a proof‐of‐concept, the capacity of a selected CrL_MOF composite to eliminate the BHET degradation products and its reusability are also investigated. The potential of these systems is envisioned in terms of improving enzyme cyclability, reducing costs along with feasible co‐adsorption of plastic byproducts and other harmful contaminants, to successfully remove them in a single step.