The surfaces of medical devices can quietly become breeding grounds for resilient bacterial colonies, which pose a significant risk to patients. These microorganisms form complex communities embedded within a self-produced extracellular matrix known as the extracellular polymeric substance, which confers enhanced resistance to antimicrobial agents and the host’s immune responses. Thus, developing methods to degrade the EPS is crucial for improving infection control in medical implants. Studies reveal that enzymes can inhibit biofilm formation by targeting essential components of the EPS, including exopolysaccharides, extracellular DNA, and proteins. Enzyme immobilization enhances enzyme reusability and stability, thereby improving biofilm eradication capabilities. They exhibit superior catalytic activity, turnover rates, and specificity in comparison to free enzymes. This systematic review examines literature from the past fifteen years (2010-2024), focusing on articles detailing enzyme immobilization techniques and their application against biofilms in the context of biomaterials and tissue engineering scaffolds. The enzyme-polysaccharide complex appears especially well suited to promote biofilm dispersal. Integrating enzyme immobilization with tissue engineering offers the possibility of improved development of infection-resistant tissue constructs.