Knee osteoarthritis is a common degenerative joint disorder that causes pain, functional limitation, and reduced quality of life. This prospective, randomized, open-label, parallel-group study was conducted to compare the clinical effectiveness and safety of Mobithron®, a multi-component oral formulation containing hyaluronic acid matrix, undenatured type II collagen, and Boswellia serrata extract, with crystalline glucosamine sulphate in patients with primary knee osteoarthritis. Participants received either Mobithron® or crystalline glucosamine sulphate for three months in addition to a standardized rehabilitation programme. Clinical outcomes were assessed at baseline, Week 2, Week 4, and Month 3. The primary outcome was change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included pain severity measured using the Visual Analogue Scale (VAS) and safety assessment through adverse event monitoring.