This review delves into the potential of hypertonic dextrose prolotherapy (HDP) as a treatment for knee osteoarthritis (KOA), a prevalent condition, that significantly impacts individuals' quality of life, particularly affecting older adults. HDP involves injecting a hypertonic dextrose solution into or around the affected joint, inducing inflammation and subsequent tissue healing. This review examines various aspects of HDP, including its mechanism of action, comparative effectiveness with other therapies, dosage, and safety considerations as well as HDP's cost-effectiveness, safety profile, and efficacy in providing pain relief and improving function. Comparative studies indicate its superior effectiveness compared to other therapies such as saline, exercise, and steroids, with persistent benefits observed over extended follow-up periods. However, careful consideration of contraindications and potential side effects is crucial. Further research is warranted to conclusively establish its safety and long-term efficacy. In summary, HDP offers a promising avenue for managing KOA, potentially improving outcomes and enhancing the quality of life for affected individuals.