Dragon's Blood (DB), a natural resin extracted from Dracaena cochinchinensis, exhibits anti-inflammatory and neuroprotective properties, but its efficacy and underlying mechanisms in ischemic stroke remain to be fully elucidated. In this study, the neuroprotective effects of DB were evaluated using both transient and permanent middle cerebral artery occlusion (tMCAO and dMCAO) models in mice. DB treatment significantly reduced infarct volume, improved neurological outcomes, and alleviated neuronal apoptosis. Transcriptomic profiling revealed that DB modulated signaling pathways related to neuroinflammation, blood-brain barrier (BBB) integrity, and actin cytoskeleton remodeling. These effects were supported by decreased Evans blue leakage, upregulated expression of tight junction proteins (ZO-1 and Claudin-5), and suppressed pro-inflammatory mediators including TNF-α, IL-1β, IL-6, and iNOS, along with increased levels of Arg-1 and IL-10. Moreover, DB downregulated disulfidptosis-related genes such as Flna, Iqgap1, Tln1, and Myh9. Molecular docking further suggested that Loureirin B, a major active constituent of DB, binds strongly to these targets, indicating a potential mechanistic link. These findings suggest that DB confers multi-target neurovascular protection in ischemic stroke by regulating inflammation, preserving BBB function, and inhibiting disulfidptosis, supporting its potential as a candidate for therapeutic development.