Inflammation is a natural defense mechanism against noxious stimuli, but chronic inflammation can lead to various chronic diseases. Neuroinflammation in the central nervous system plays an important role in the development and progression of neurodegenerative diseases. Polyphenol-rich natural products, such as Ecklonia cava (E. cava), are known to have anti-inflammatory and antioxidant properties and can provide treatment strategies for neurodegenerative diseases by controlling neuroinflammation. We investigated the effects of an E. cava extract on neuroinflammation and neurodegeneration under chronic inflammatory conditions. Mice were pretreated with E. cava extract for 19 days and then exposed to E. cava with lipopolysaccharide (LPS) for 1 week. We monitored pro-inflammatory cytokines levels in the serum, inflammation-related markers, and neurodegenerative markers using Western blotting and qRT-PCR in the mouse cerebrum and hippocampus. E. cava reduced pro-inflammatory cytokine levels in the blood and brain of mice with LPS-induced chronic inflammation. We also measured the activity of genes related to neuroinflammation and neurodegeneration. Surprisingly, E. cava decreased the activity of markers associated with inflammation (NF-kB and STAT3) and a neurodegenerative disease marker (glial fibrillary acidic protein, beta-amyloid) in the cerebrum and hippocampus of mice. We suggest that E. cava extract has the potential as a protective agent against neuroinflammation and neurodegenerative diseases.