AbstractMusculoskeletal spine disorders, especially low back pain, induce enormous amounts of stress and financial burden on individuals and healthcare systems throughout the world. Disorders of the facet joints in the lumbar spine are the most predominant cause of back pain, resulting in facet joint syndrome (FJS). Conventional treatments for FJS are short-lived and have limitations and side effects. Thus, safer and more effective alternatives that can reduce pain and improve patient-reported outcomes are needed. Recently, the utilization of biologics, including the ones derived from perinatal tissue such as amniotic membrane (AM) and umbilical cord (UC), has significantly increased for regenerative medicine applications. This manuscript summarizes the outcomes of preclinical and clinical studies utilizing AM and/or UC for FJS. We identified no preclinical studies and 3 retrospective studies utilizing the search terms “amniotic membrane” and/or “umbilical cord” and “facet joint syndrome”. The administration of AM + UC is safe and potentially efficacious for patients with FJS. However, more preclinical studies and appropriately powered, multi-center, prospective non-randomized and randomized controlled studies with longer follow-up are warranted to further evaluate the efficacy of AM + UC to justify its clinical use.