Objective: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis.Study design and setting: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand.Methods: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of ≥5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded.Results: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively).Conclusions: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.