Gy-CATH is an anionic antimicrobial peptide that activates the MAPK and NF-κB signaling pathways, increasing levels of phosphorylated ERK, p38, JNK, p65, and IκBα. It upregulates expression levels in three physiological anticoagulant pathways. While Gy-CATH does not exhibit direct antimicrobial activity, it significantly prevents infections caused by Staphylococcus aureus, Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA) in mice. Additionally, Gy-CATH suppresses platelet aggregation induced by ADP, collagen, and PMA. It displays strong immunomodulatory activity, enhancing macrophage and neutrophil-mediated bactericidal functions. Furthermore, Gy-CATH markedly reduces lung fibrin deposition and prevents thrombosis in mice.