Hyaluronic acid from Liparis tessellatus eggs (HALTE) was grafted with caffeic acid (CA-g-HALTE), ferulic acid (FA-g-HALTE), gallic acid (GA-g-HALTE), and nisin (Nisin-g-HALTE) and investigated for their anti-inflammatory and antioxidant potential in lipopolysaccharides-stimulated RAW 264.7 mouse macrophages. Nitric oxide (NO) generation and prostaglandin E 2 activity were measured after treatment with the grafted HALTE samples. All grafted HALTE samples exhibited more antioxidant activity against 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals than 2,2-diphenyl-1-picrylhydrazyl radicals. Nisin-g-HALTE showed the least antioxidant activity. Additionally, the NO assay results showed that all grafted samples had no cytotoxic effect on RAW 264.7 macrophages and reduced macrophage activity after treatment. The most effective concentrations of CA-g-HALTE and FAg-HALTE were found to be above 100 μg/mL. Increased sample concentration resulted in increased activity except with Nisin-g-HALTE at 100 μg/mL. CA-g-HALTE, FA-g-HALTE, GA-g-HALTE, and Nisin-g-HALTE were found to have antioxidant and anti-inflammatory potential, which can be further explored for use in food, cosmetic, nutraceutical, and biomedical applications.