Background: Knee osteoarthritis (OA), a common degenerative joint disorder, significantly impairs quality of life due to pain and functional limitations. Non-surgical interventions like lateral shoe wedging and quadriceps strengthening exercises are increasingly considered viable options for managing OA symptoms. Objective: To assess the efficacy of lateral shoe wedges, both alone and in combination with quadriceps strengthening exercises, in treating medial knee OA. Methods: In this randomized controlled trial, 60 adults with medial knee OA were assigned to one of three groups: Group A received only lateral shoe wedges; Group B received lateral shoe wedges and quadriceps strengthening exercises; Group C received lateral shoe wedges with lifestyle modifications. Measurements for pain, stiffness, and physical function were taken using the Numeric Pain Scale and WOMAC scale at baseline, 8 weeks, and 16 weeks. Results: By Week 16, Group A (wedge only) reported a 70% compliance rate, with no significant changes in WOMAC stiffness and physical function scores. Group B (wedge & exercise) showed an 80% compliance rate, with pain scores reducing from 2.50±0.945 to 1.40±1.231 and significant improvements in WOMAC stiffness (1.40±1.231) and physical function (1.50±1.147). Group C (wedge & lifestyle modification) achieved a 100% compliance rate, with moderate improvements in all measured parameters. Conclusion: The study concludes that the combination of lateral shoe wedging and quadriceps strengthening exercises (Group B) was most effective in alleviating pain and improving physical function in patients with medial knee OA. This suggests that a multimodal approach may be superior to singular interventions for managing OA symptoms.