Background: Most trials on symptom-modifying effects of glucosamine are limited to administration through oral route with dearth of empirical data on the use of electromotive force. Objective: The study determined the effects of glucosamine sulphate (GS) iontophoresis (IoT) on radiographic parameters of patients with knee osteoarthritis (OA). Methods: Fifty-three patients were randomly assigned to three groups. About 1[Formula: see text]g each of GS was administered using IoT and cross-friction massage (CFM) for participants in groups 1 (IoT) and 2 (CFM), respectively. Group 3 ((Combined therapy) CoT) received 1[Formula: see text]g of GS using both IoT and CFM. Interventions were twice a week for 12 weeks. Analysis of variance (ANOVA) was used to analyze the data ([Formula: see text]). Results: After 12 weeks, the medial joint space width (JSW) of the CFM group was significantly higher than that of IoT and CoT groups ([Formula: see text] and [Formula: see text]). Lateral JSW of IoT group was significantly higher than both CFM ([Formula: see text]) and CoT groups ([Formula: see text]). There were significant decreases in pain intensities; increase in knee flexion and physical functions across the groups ([Formula: see text]; [Formula: see text], respectively). Conclusion: It was concluded that there were significant decreases in the degenerative changes at the knee joint.