Infections and thrombus formation are major concerns for the success of blood‐contacting medical devices. Antimicrobial coatings based on antimicrobial peptides (AMPs) are described as promising strategies to fight biomaterial‐associated infections. However, their efficiency in the presence of plasma and their effect on platelets adhesion/activation, essential for blood contact applications, is not known. In this work, the AMP cecropin–melittin (CM) is covalently immobilized onto polyurethane (PU) films envisaging a coating for intravascular catheters. Immobilization is done by dip‐coating of a layer of gold nanoparticles (Au NPs) functionalized with NH2 and COOH terminated polyethylene glycol (PEG). Surfaces characterized using scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), quartz crystal microbalance with dissipation (QCM‐D), and colorimetric assays reveal a stable and homogeneous coating distribution. CM coating significantly reduces Staphylococcus epidermidis adhesion to PU films (≈80% in PBS). Its bactericidal activity is not affected in the presence of 1% human plasma (hPlasma) proteins with 65% reduction on viable bacteria comparing to PU. Moreover, CM coating is able to prevent platelet adhesion/activation to PU films (≈95% in PBS). This effect is also observed when surfaces are precoated with hPlasma. Overall, the developed antimicrobial coating demonstrates great potential to prevent bacterial infections on PU devices without instigating platelet adhesion/activation.