Background: Uncaria tomentosa is a vine commonly known as cat’s claw or ‘uña de gato’ (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. Purpose: The aim of this study was to determine the proposed anti‐inflammatory properties of cat’s claw. Specifically: (i) does a bark extract of cat’s claw protect against oxidant‐induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. Methods: Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 μM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF‐κB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). Results: The administration of UG (100 μg/mL) attenuated (P < 0.05) peroxynitrite‐induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat’s claw inhibited lipopolysaccharide‐induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF‐κB. Cat’s claw markedly attenuated indomethacin‐enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. Conclusions: Cat’s claw protects cells against oxidative stress and negated the activation of NF‐κB. These studies provide a mechanistic evidence for the widely held belief that cat’s claw is an effective anti‐inflammatory agent.