In recent years, artificial placenta systems have been developed for the clinical treatment of infant respiratory distress syndrome (RDS). Their use requires systemic anticoagulation to prevent clotting during treatment. However, this approach significantly increases the risk of intracranial hemorrhage in premature infants. Therefore, suitable surface modification is needed to eliminate the need for systemic anticoagulants. We have developed a dual-modification method based on an antithrombin-heparin complex (ATH) and tissue plasminogen activator (t-PA) using polydopamine as a surface linker to attach the molecules to polydimethylsiloxane (PDMS) surfaces. The resulting materials were previously shown to have enhanced anticoagulant properties, believed to be through a synergistic effect between the two molecules. The polydopamine-linked coating can be used with a variety of materials and shows promise in applying these modifications to complex structures. Here, we translated this modification method to a PDMS microfluidic oxygenator system that constitutes the artificial placenta. Scanning electron microscopy (SEM) demonstrated successful modification of the microfluidic units, and radiolabeling data showed that the dual bioactive modification was uniformly distributed within the device. The surface density and stability of the immobilized biomolecules were similar to those found previously for the same modifications on simple PDMS discs, suggesting that they should have similar anticoagulant effects in the oxygenator. This was confirmed using human plasma and whole blood, in which the dual-modified oxygenator showed a significant increase in anticoagulant properties. It was also demonstrated that the surface modifications did not affect the oxygenator’s gas exchange capacity. These results indicate that this bioactive surface modification approach shows promise for use in clinical artificial placenta systems.