SAP15 (Synthetic anti-inflammatory peptide 15) is a synthetic peptide composed of 15 amino acids, derived from human beta-defensin 3, with the ability to penetrate cells and mitigate intracellular inflammation. It achieves its anti-inflammatory effects by blocking the phosphorylation of HDAC5, which in turn reduces NF-κB p65 phosphorylation. In macrophages stimulated with LPS, SAP15 suppresses the phosphorylation of both HDAC5 and NF-κB p65, demonstrating potent anti-inflammatory actions. Furthermore, treatment with SAP15 in LPS-induced chondrocytes elevates aggrecan and type II collagen levels while reducing osteocalcin expression. This peptide is valuable for exploring inflammation regulation and the development of anti-inflammatory therapies in biomaterials.