This study was with a view to comparing the effective means of alleviating pain and improving physical functions in patients with knee osteoarthritis using quadriceps strengthening exercises, glucosamine and chondroitin sulphate iontophoresis. Seventy-eight participants with grade II knee OA were purposively selected and randomly assigned to three groups using fish bowl technique. Group one participants received 1g of glucosamine sulphate (GS) through iontophoresis while group two received 1g of chondroitin sulphate (CS) iontophoresis (40mA- min as dosage) using trans-arthral electrode placement technique twice a week, for 12 weeks. Group three participants had intervention in the form of quadriceps muscle strengthening exercise (1RM, 10 reps and 3 sets), which was a baseline treatment for all the groups. Pain intensity, active knee range of motion and physical function were assessed. Descriptive statistics, ANOVA and Kruskal-wallis test were used to analyze the data. Alpha level was set at p ≤ 0.05. The three modes of interventions significantly alleviated pain (p = 0.001), improved the Functional Activity Level and active ranges of motion (p = 0.001) in the groups after 12 weeks. Although, the administration of Quadriceps strengthening exercise alone, significantly improved the Functional Activity Level than Chondroitin sulphate iontophoresis and Glucosamine sulphate (H = 19.89, p = 0.001). However; there was no significant difference in the active range of motion across the 3 groups. In conclusion, Quadriceps strengthening exercise, Glucosamine and Chondroitin sulphate iontophoresis were effective in alleviating pain, enhancing range of motions and improving physical functions. However, Quadriceps strengthening exercise showed higher efficacy compared to others.