Biofluid-contacting medical devices are highly prone to biofouling, resulting in thrombus formation and bacterial biofilm growth, diminish device functionality, and posing very serious health implications. Traditional antifouling strategies, using hydrophilic polymers and heparin coatings, often show limited stability and reduced bioactivity over time. Lubricant-infused surfaces (LIS) have emerged as a promising alternative due to their stability and broad-spectrum repellency. However, traditional method of fabricating LIS relies on multi-step processes, including pre-coating the devise surface through chemical vapor deposition (CVD) or liquid-phase deposition (LPD) to create a silicon- or fluorine-based layer, followed by lubricant infusion. These complicated steps limit LIS application to surface layers, often compromising performance under mechanical stress. This thesis presents a new, simplified approach to overcome these limitations by developing a bulk-modified poly(vinyl alcohol) (PVA) film that inherently supports LIS properties without requiring an additional coating step. These super-flexible lubricant-infused silane-crosslinked PVA samples were fabricated by the crosslinking of the PVA chains by n-propyltrichlorosilane (nPTCS), followed by infusion with silicone oil as a lubricant. This modification creates a chemical affinity between the film and the lubricant directly within the bulk and surface of the material, enabling lubricant infusion at any stage, simplifying the process, and ensuring long-lasting LIS functionality. Comprehensive analysis of the films showed that the Lubricant-infused silane-crosslinked PVA films inhibit blood and plasma clot formation significantly, along with a reduction in bacterial adhesion. More importantly, these films present enhanced mechanical performance in elasticity and flexibility, compared to an unmodified PVA films. This method provides a versatile method for developing high-performance antifouling biointerfaces, providing improved performance and durability under mechanical stress and representing a significant advancement over traditional antifouling strategies.