Osteoarthritis (OA) is a joint disease that most commonly accompanied with pain and joint deformity which eventually leads to disability. Burden of OA will be accounted second in women and fourth in men in Iran. Most therapies of knee osteoarthritis are symptomatic treatment. This study was designed to assess the efficacy of Glucosamine and Chondroitin sulfate in complete dose and one – third dose as a low cost protocol on treating of knee OA. Study was performed as a randomized double blind clinical trial. Symptomatic knee OA cases at Kellgren – Lawrence based stages I, II and III were enrolled in study following exclusion of systemic disease as well as joint disease. Cases were divided into 3 groups: complete dose treatment (Group I), One – third dose treatment (Group II) and placebo user (Group III). Then cases were followed for 12 weeks via Visual Analog Scale (VAS) and Western Ontario and McMaster universities (WOMAC) questionnaires associated with subsequent statistically analyzes. Statistically significant differences in the rate decline of pain, stiffness, functionality and eventually total scores as well as VAS scores were observed between both treatment groups (Group I and II) and placebo users (Group III) without any Statistically significant differences between themselves (Group I and Group II). Due to effects of Glucosamine and Chondroitin sulfate at one–third dose level recommends for OA as a low cost protocol in association with weight loss and muscles physiotherapy as well as healthy use of joints.