Background: Osteoarthritis (OA) is the most common joint disorder without any curative treatment so, pharmacologic and nonpharmacologic modalities are used to improve pain and disability. Objectives: This is a study for evaluation of the efficacy and safety of Elaeagnus angustifolia and ginger extracts in patients with osteoarthritis of the knee. Patients and Methods: This randomized double-blind clinical trial study carried out on 80 outpatients with knee OA. The patients were randomized to take 200 mg extract of E. angustifolia and ginger or placebo. Knee radiography, serum biochemistry and blood pressure were recorded at baseline and the patients were evaluated for pain intensity, patient and physician global assessment of efficacy, and analgesic use in the past week. The statistical analysis was done using χ 2 and t-test for comparing the mean values of patients at baseline and after intervention. Results: Sixty-one patients completed the study. Of all 97.5% of patients were females and the mean of BMI was 30 ± 4.5 kg/m 2. An entry 53 (66.2%) of patients were receiving analgesics. Eight weeks after the intervention, the patients in drug group had more improvement in pain intensity according to visual analogue scale (VAS) (P = 0.02) and the physician evaluation according to a 4-scale scoring system (P = 0.03), but the analgesic consumption for pain control was not different. Serum biochemistry and ESR did not change after the intervention. Conclusions: The results of this study suggest that combination of E. angustifolia and ginger extracts are safe and may have some efficacy in patients with knee OA.