Alkylresorcinols (ARs) are phenolic lipids, found in the bran layer of cereals such as rye. They are natural antioxidants that confer many health benefits. In this study, ARs were extracted from Hazlet rye bran and analyzed for their in vitro antioxidant and anti-inflammatory activities and in vivo antiobesity and antioxidant activities. In vitro studies showed that rye bran ARs have higher antioxidant activity than those from wheat and oat bran. ARs also exhibited anti-inflammatory activity by inhibiting the inflammatory mediator nitric oxide (NO), and gene expression of iNOS and COX-2. ARs did not exhibit antiobesity activity in CF-1 mice fed a 60% high fat (HF) diet but showed in vivo antioxidant activity in the liver using the oxygen radical absorbance capacity (ORAC) assay. In heart tissue, ARs exhibited higher antioxidant activity than the HF control diet, using the ORAC, superoxide dismutase (SOD), and glutathione assays, but results were not significant.