Objective <p>This study aims to evaluate the effectiveness of combined antibiotic therapy and isometric exercise in treating knee synovitis in patients with osteoarthritis (OA) and type 2 diabetes mellitus (T2DM). Given the common coexistence of OA and T2DM, this research seeks to understand the influence of these treatments on inflammation, pain, and functional limitations in this patient population.</p> Methods <p>This retrospective study involved 64 patients diagnosed with knee synovitis and T2DM at a physical therapy and rehabilitation clinic. Patients were treated with nonsteroidal anti-inflammatory drugs and antibiotics over a combined period of 24&#xa0;days and underwent isometric exercises. Pain and function were assessed using the Lequesne Algo-Functional Knee Index (LAFI) and Douleur neuropathique 4 (DN4) pain questionnaire.</p> Results <p>Significant improvements were observed in both LAFI and DN4 scores post-treatment (<i>p</i> &lt; 0.001). Correlations between diabetes duration, body mass index, and pain levels were strong, highlighting the influence of metabolic factors on knee synovitis. Symptoms such as night pain, morning stiffness, and pain with walking improved significantly, and functional abilities like walking distance and stair climbing were enhanced after treatment.</p> Conclusion <p>The combined use of antibiotic therapy and isometric exercise significantly alleviated symptoms in patients with knee synovitis, suggesting a promising approach for managing OA in T2DM patients. Further research, particularly randomized controlled trials, is needed to confirm these findings and refine treatment protocols.</p>