Objectives <p>Polydeoxyribonucleotide (PDRN), extracted from salmon, has been shown to promote tissue repair, reduce inflammation, and enhance cartilage regeneration through A2A receptor activation. It is considered effective for treating musculoskeletal disorders; however, clinical research and standardized treatment protocols remain insufficient.</p> Methods <p>A total of 17 studies on the use of PDRN pharmacopuncture for musculoskeletal disorders were analyzed. Ultrasound guidance was the most commonly used method, and NRS (Numeric Rating Scale) and VAS (Visual Analog Scale) were the primary assessment tools employed.</p> Results <p>PDRN pharmacopuncture suggested significant pain reduction and functional improvement in various musculoskeletal disorders, including cervical, upper limb, lumbosacral, and lower limb conditions, when administered under ultrasound guidance. Significant improvements were observed in NRS and VAS scores, and PDRN injections showed long-term pain relief and tissue regeneration effects in tendinopathy, neuropathy, and arthritis.</p> Conclusion <p>PDRN pharmacopuncture has suggested tissue regeneration and anti-inflammatory effects in musculoskeletal disorders, with enhanced precision and effectiveness through ultrasound-guided administration. Unlike other pharmacopunctures that focus on pain relief and inflammation control, PDRN promotes tissue regeneration at the cellular level, offering a distinctive therapeutic advantage. Further research is needed to verify the long-term effects of PDRN and its combined use with other pharmacopunctures.</p> Graphical abstract <p></p>