Inflammation is the essential process for responding to pathogenic infections, cancer, autoimmune diseases, and other inflammatory diseases. Oxidative stress leads to inflammatory responses. This study aims to evaluate whether the polyphenols in the Elaeagnus latifolia (EL) fruit water extract ameliorate inflammation. RAW 264.7 macrophages were stimulated with lipopolysaccharide with or without Elaeagnus latifolia (EL) extract. Quantitative PCR and ELISA were used to examine the gene expression and cytokines. Our results showed that EL extract-treated activated cells significantly decrease ROS and Nitric oxide levels by reducing the p22phox and iNOS expression and lowering cytokine-encoding genes, including IL-6, PG-E2, TNF-α relative to the LPS-activated macrophages. Furthermore, we observed the protein profiling between LPS-stimulated cell with or without EL extract. Our data establish that EL extract has antioxidant and anti-inflammatory activities and provide evidence that EL extract may be a protective compound for inflammatory diseases.