Network pharmacology and experimental validation indicated that DSS exerts its anti-neuroinflammatory effects by inhibiting JAK2 and STAT3 phosphorylation, reducing their nuclear translocation, and consequently suppressing Th17 differentiation and pro-inflammatory cytokine production.<h4>Conclusion</h4>DSS is a promising candidate for AD treatment, with neuroprotective and cognitive-enhancing properties mediated through immunomodulation and JAK2/STAT3 pathway inhibition. Here, STAT3 is linked to Alzheimer disease.