AIM: To overcome the limitations of sodium alginate hydrogel (SAH), including its slow degradation and limited bioactivity in wound healing applications, we developed a functionalized hydrogel (SAQM) incorporating Mg2? and quercetin (Que). We further conducted a systematic evaluation of its roles and underlying molecular mechanisms in modulating neutrophil-mediated inflammatory responses and oxidative stress. METHODS: SAH and SAQM were prepared via ionic crosslinking induced by CaCl2. Morphology was characterized by SEM, mechanical properties were analyzed via rheometry, and component release was quantified using ICP-AES/UV spectrophotometry. In vitro evaluation employed a dHL60 neutrophil model stimulated with LPS. Inflammatory markers and NF-kB pathway activation were assessed by RT-qPCR and Western blot, while ROS generation was measured via flow cytometry. RESULTS: In vitro experiments demonstrated sustained release of Mg2+ and Que from SAQM. SEM and rheological analyses revealed comparable gelation and microstructure between SAQM and SAH, but SAQM showed significantly reduced swelling and enhanced degradation rates. Biocompatibility studies confirmed negligible cytotoxicity toward neutrophils. In LPS-induced inflammation, SAQM markedly suppressed pro-inflammatory cytokine expression and ROS production. Compositional analysis indicated Mg2+ primarily mediated anti-inflammatory effects, while Que contributed to antioxidant activity. Notably, SAQM treatment inhibited LPS-induced activation of the canonical NF-kB pathway, suggesting its anti-inflammatory mechanism involves NF-kB suppression. CONCLUSION: SAQM combines improved degradability with dual anti-inflammatory and antioxidant properties, representing a promising immunomodulatory hydrogel dressing for clinical applications.