Gold-induced cytokine (GOLDIC) is a novel orthobiologic approach utilizing gold particles to produce a serum rich in immunoregulating cytokines and growth factors, which is being explored for its potential in tissue regeneration and treating musculoskeletal issues like knee osteoarthritis (OA). This study aims to review its mechanism of action along with the outcomes of in vitro, preclinical, and clinical studies, with a secondary focus on documenting clinical trials related to its use in OA of the knee. A systematic search was conducted in four databases (Embase, Scopus, PubMed, Web of Science) for studies on GOLDIC therapy for knee OA, using specific keywords related to knee anatomy and OA. In vitro studies demonstrated that goldcontaining compounds reduce nitric oxide production in chondrocytes, mitigating catabolic processes. Preclinical trials in horses with lameness showed significant symptom improvement. Clinical studies reported substantial improvements in pain, function, and joint homeostasis, with reduced synovial effusion and cytokine modulation following GOLDIC therapy. GOLDIC therapy, in addition to orthopedic indications such as for the management of OA of the knee, has also been investigated in non-orthopedic settings with early promising results. However, more research is needed to fully understand its mechanism of action and establish its clinical utility.