BACKGROUND: Knee osteoarthritis is a common degenerative disease characterized by cartilage destruction and inflammatory changes in the synovial membrane. Obesity and metabolic syndrome are significant risk factors that exacerbate inflammatory processes and contribute to the progression of osteoarthritis. Modern treatment methods include both pharmacological agents and non-pharmacological approaches such as aerobic exercise. AIM: To evaluate and compare the effectiveness of diacerein combined with aerobic physical activity (Nordic walking) in the comprehensive treatment of knee osteoarthritis. MATERIALS AND METHODS: The study involved 65 patients aged 45 to 70 years with knee osteoarthritis and metabolic syndrome. The participants were divided into three groups. The first group received diacerein (Artrocare); the second group was engaged in Nordic walking; the third group – a combination of these methods. The visual analog scale of pain, Western Ontario and McMaster University Osteoarthritis (WOMAC) index, quality of life (Short Form-36), glycated hemoglobin levels, and other biochemical parameters were assessed over 16 weeks of observation. RESULTS: The study demonstrated statistically significant reductions in pain levels and improvements in functional parameters in all the groups. The greatest improvements were observed in the group receiving combined therapy. The method showed a significantly positive impact on quality of life and reduced the need for analgesics in comorbid patients. Additionally, the patients with metabolic syndrome showed improved biochemical parameters with the combination of diacerein and Nordic walking. CONCLUSIONS: The combined use of diacerein and Nordic walking is an effective and safe method for treating knee osteoarthritis, particularly in patients with metabolic syndrome. This approach significantly reduces pain, improves joint function, and enhances overall quality patient’s life.