PurposeOsteoarthritis (OA) is an age-related disease caused by the wear and tear of the joints. Presently, there is no known cure for OA, but its management involves the use of high doses of pain killers and antiinflammatory agents with different side and dependency effects. Alternative management strategies involve the use of high doses of glucosamine-chondroitin (GC). This study was carried out to evaluate the efficacy of Q-Actin™, an aqueous extract of Cucumis sativus (cucumber; CSE) against GC in the management of moderate knee OA.Patients and methodsOverall, 122 patients (56 males and 66 females) aged between 40 and 75 years and diagnosed with moderate knee OA were included in this randomized double-blind, parallel-group clinical trial that took place in three different centers. The 180 day intervention involved two groups of 61 participants in each: the GC group, which received orally the generally prescribed dose of 1,350 mg of GC twice daily and the CSE group, which received orally10 mg twice daily of CSE. The Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog scale, and Lequesne’s Functional Index were used to evaluate pain, stiffness, and physical function of knee OA in participants at baseline (Day 0) and on Days 30, 60, 90, 120, 150, and 180.ResultsIn the CSE group, the WOMAC score was decreased by 22.44% and 70.29% on Days 30 and 180, respectively, compared to a 14.80% and 32.81% decrease in the GC group. Similar trends were observed for all the other pain scores. No adverse effect was reported during the trial period.ConclusionThe use of 10 mg CSE, twice daily, was effective in reducing pain related to moderate knee OA and can be potentially used in the management of knee pain, stiffness, and physical functions related to OA.