Oxidative stress and inflammation are interlinked processes that seem to play an important role in aging. The present work aimed to test the antioxidant and anti-inflammatory activity of ethanolic Mahonia aquifolium leaves and bark extracts in an experimental acute inflammation. Six polyphenols and four alkaloids were measured by HPLC. The radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. Inflammation was induced in rat with turpentine oil. Anti-inflammatory activity was evaluated with serum nitric oxide (NOx) and tumour necrosis factor alpha (TNF-alpha), and oxidative stress with total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrotyrosine (3NT), malondialdehyde (MDA) and total thiols (SH). Extracts were administrated orally (100%, 50%, 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The most abundant polyphenol was chlorogenic acid, and alkaloids were identified only in the bark extract. The DPPH assay showed good results, except for the bark extract. All extracts decreased NOx, TOS, 3NT, and increased SH. TNF-alpha was reduced, and TAR was increased only by the leaves extract. MDA was not influenced. Our findings suggest that M. aquifolium leaves and bark extracts have anti-inflammatory and antioxidant effects that support the use in primary prevention of the “inflammaging” process.