Regenerative injection therapy and low level laser therapy are alternative remedies known for their success in the treatment and symptomatic management of chronic musculoskeletal conditions. In response to the growing demand for alternative therapies in the face of the opioid epidemic, the authors conduct a literature review to investigate the potential for prolotherapy and LLLT to be used adjunctively to manage chronic osteoarthritis (OA). OA is a degenerative chronic musculoskeletal condition on the rise in North America, and is frequently treated with opioid medications. The regenerative action of prolotherapy and pain-modulating effects of LLLT may make these two therapies well-suited to synergistically provide improved outcomes for osteoarthritis patients without the side effects associated with opioid use. A narrative descriptive review through multiple medical databases (Google Scholar, PubMed, and MedLine) is conducted, restricted by the use of medical subject headings. 71 articles were selected for reading in full, and 40 articles were selected for use in the study after reading in full. A review of the literature revealed good clinical results in the use of prolotherapy and LLLT separately to manage chronic musculoskeletal pain due to osteoarthritis and other chronic conditions. It is also recognized in the literature that prolotherapy works most effectively when used adjunctively with other treatments. Downsides to the use of prolotherapy include mild side effects of pain, stiffness and bruising and potential adverse events as a result of injection. This study is limited by the lack of clinical trials available involving both LLLT and prolotherapy injections used adjunctively, and by the low number of high impact literature concerning the treatment of (specifically) osteoarthritis by alternative methods. The authors suggest that practicing health care providers consider utilizing LLLT and prolotherapy together as a supplementary method in the management of chronic pain due to osteoarthritis, to minimize the long-term prescription of opioids and emphasize a less invasive treatment for this debilitating condition.