‘Liquid-like’ solid surfaces that overcome the limitations of lubricant-infused slippery surfaces, have garnered attention as passive antibiofouling coatings for biomedical applications. However, lack of intrinsic bioactivity limits its ability to eradicate planktonic microbes and prevent platelet activation—leading to microbial contamination and thrombosis that results in device occlusion, and patient mortality. Thus, in this work, we exploit the passively antifouling properties of ‘liquid-like’ solid surfaces and integrate it with the vasodilatory, bioactive gasotransmitter nitric oxide (NO), secreted by the endothelium to create a novel combinatorial antibiofouling platform. Bio-inspired NO donor molecules offer both antibacterial and antithrombotic functionalities, addressing the limitations of conventional antibiotic therapies and metal ion-based bioactive coatings. But the reduced efficiency of NO towards protein repellence still requires the integration with a secondary antifouling mechanism. Therefore, co-condensing the molecular spacer (tetramethyl orthosilicate) and low-surface-energy organosilane (n-octyltriethoxysilane) onto NO-releasing medical-grade polymers, we engineer an omniphobic ‘liquid-like’ solid coating on bioactive polymers exhibiting integrative bioactive and passive antifouling properties. To our knowledge, this is the first experimental quantification of such a cytocompatible and hemocompatible combinatorial polymer that eliminates surface-adhered and planktonic bacterial growth, resists long-term biofilm formation, repels human fibrinogen adhesion, and inhibits platelet adhesion/activation. Our results demonstrate that the combinatorial polymeric material significantly outperforms the individual passive or bioactive approaches. We anticipate that this innovative platform, applicable to polymers used in medical devices such as catheters, cannulas, and extracorporeal circulation circuits, showcases the potential of ‘liquid-like’ surfaces with NO for in vivo applications.