This study aimed to evaluate the effectiveness of prolotherapy compared to other non-surgical approaches in the treatment of knee osteoarthritis (OA). The investigation was conducted as a randomized controlled experiment lasting for 12 months. It involved persons who had been diagnosed with knee osteoarthritis (OA). The individuals were randomly assigned to either undergo prolotherapy, which involved receiving hypertonic dextrose injections at weeks 0, 4, and 8, or receive non-surgical therapies according to known clinical procedures, including physical therapy and injections of hyaluronic acid. The study's primary metrics for evaluating success were the reduction of pain (quantified using the Visual Analog Scale) and enhancement of functional capabilities (measured by the Western Ontario and McMaster Universities Osteoarthritis Index). Additional metrics considered were changes in knee joint flexibility, life quality (evaluated via the SF-36 questionnaire), and the occurrence of adverse events. The findings indicated a notable decrease in pain and functional improvements for those treated with prolotherapy in comparison to the non-surgical group, without the report of any severe adverse effects. The research suggests prolotherapy as a potentially superior treatment for knee OA, evidenced by its significant benefits in alleviating pain and enhancing function, though it acknowledges the study’s limitations like the brief follow-up duration and limited sample size, highlighting the necessity for additional studies to corroborate these results.