Background: Osteoarthritis (OA) is a chronic debilitating degenerative joint disease characterized by cartilage degradation and synovial inflammation exhibited by clinical symptoms such as joint swelling, synovitis, and inflammatory pain. Present day pain relief therapeutics heavily relies on the use of prescription and over the counter nonsteroidal anti-inflammatory drugs as the first line of defense where their long-term usage causes detrimental gastrointestinal and cardiovascular-related side-effects. As a result, the need for evidence based safer and efficacious alternatives from natural sources to overcome the most prominent and disabling symptoms of arthritis is a necessity. Materials and Methods: Describe the anti-inflammatory and analgesic effect of UP3005, a composition that contains a standardized blend of two extracts from the leaf of Uncaria gambir and the root bark of Morus alba in carrageenan-induced rat paw edema, abdominal constriction (writhing's) and ear swelling assays in mouse with oral dose ranges of 100-400 mg/kg. Results: In vivo, statistically significant improvement in pain resistance, and suppression of paw edema and ear thickness in animals treated with UP3005 were observed compared with vehicle-treated diseased rats and mice. Ibuprofen was used a reference compound in all the studies. In vitro, enzymatic inhibition activities of UP3005 were determined with IC50 values of 12.4 μg/ml, 39.8 μg/ml and 13.6 μg/ml in cyclooxygenase-2 (COX-1), COX-2 and lipoxygenase (5-LOX) enzyme activity assay, respectively. Conclusions: These data suggest that UP3005, analgesic and anti-inflammatory agent of botanical origin with balanced dual COX-LOX inhibition activity, could potentially be used for symptom management of OA.