Methods: First, we explored the key pathogenesis of ALF and the induction pathway of MMP-9 in the early stages of injury. Next, we examined the pathological role of MMP-9 in the major complications that occur during the progression of ALF. Subsequently, we compared MMP-9 inhibition strategies between Western and natural product based approaches, analyzing the pros and cons of each approach. Finally, we explored clinical cases of actual fusion therapy to assess its potential. Results: Under normal physiological conditions, MMP-9 plays a positive role in regulating hepatocyte regeneration and neuronal plasticity. However, when pathologically overexpressed during ALF progression, it induces increased vascular permeability, Extracellular Matrix (ECM) degradation, and Blood-Brain-Barrier (BBB) disruption, which are closely associated with the development of various complications, including HE, liver fibrosis, and multi-organ failure. Therefore, MMP-9 was identified as a key factor linking the development of ALF and its complications. In the case of MMP inhibitors from western treatments, such as GM6001, they can suppress inflammation and liver damage by directly inhibiting MMP-9, but there is a side effect of worsening liver fibrosis. In the case of natural product extracts such as beta-asarone, it can induce an anti-inflammatory effect through inhibition of inflammatory cytokines, therefore reducing MMP-9 expression. However, there is the side effect of relatively low bioavailability and toxicity such as liver cancer when used in excess. Conclusion: Both Western and natural product-based monotherapy strategies each have limitations, and some also raise concerns about adverse effects. Therefore, introducing a Western-Korean fusion treatment from an integrative medicine perspective has the potential to simultaneously enhance treatment efficacy and safety. However, the specific mechanism of action and clinical evidence for this fusion treatment strategy are still unexplored, so multidisciplinary follow-up studies are needed to elucidate them.