Neutrophils utilize a specialized form of cell death, Neutrophil Extracellular Traps (NETs), to kill and trap invading pathogens; however, dysregulated NET release (NETosis) can drive tissue damage and fibrosis at host–biomaterial interfaces. Manuka honey exhibits potent antibacterial and emerging anti-inflammatory properties within and outside electrospun vascular tissue-engineering templates. Because current small-diameter vascular graft materials do not adequately resolve neutrophil-driven acute inflammation, they often fail, and no synthetic grafts below 4 mm in diameter are currently approved for clinical use, leaving a substantial unmet need in cardiovascular medicine. This investigation tested two central hypotheses: (1) incorporating Manuka honey into polydioxanone (PDO) touch-spun vascular templates would reduce NET formation, and (2) the touch-spinning method, which uses mechanical rather than electrical forces to draw fibers, would preserve Manuka honey’s bioactivity more effectively than traditional biomaterial fabrication approaches. Templates were fabricated from 185 mg/mL polydioxanone (PDO) containing 0%, 0.1%, 1%, or 10% Manuka honey and co-cultured with primary human neutrophils for 4 hours. NETosis was quantified from culture supernatants using a myeloperoxidase (MPO) assay. Mechanical properties were evaluated following ANSI/ AAMI standards for vascular graft prostheses and compared across Manuka concentrations relative to 0% controls and native blood vessels. Findings from this study demonstrate that Manuka honey can be integrated into touch-spun vascular templates without compromising the required mechanical properties. Moreover, Manuka-incorporated templates retained Manuka honey’s neutrophil-modulating effects more effectively than electrospun counterparts. Finally, the sustained release profile of Manuka honey from these grafts aligns well with the acute, neutrophil-dominant inflammatory window following biomaterial implantation.