Abalone is a marine gastropod and an important fishery and food industrial resource that is massively maricultured in Asia, Africa, Australia, and America. However, the health beneficial effects of abalone have rarely been reported. In the present study, we examine the antioxidant and anti-inflammatory effects of abalone Haliotis discus hannai in macrophage cells. The results showed that abalone intestine digest (AID) has antioxidant activities against lipid peroxidation, ROS stress and DNA damage in H2O2-treated RAW264.7 macrophages. In the lipopolysaccharide (LPS)-induced macrophages, AID suppresses LPS-induced production of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. It also significantly reduced the generation of proinflammatory cytokines, such as interleukin (IL-1β), tumor necrosis factor (TNF)-α, and IL-6. Furthermore, AID significantly suppresses the phosphorylation of mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. These results indicated that AID inhibits oxidative damage by ROS and LPS-induced inflammatory response via blocking the MAPK signaling pathway in murine macrophages. The potent antioxidant and anti-inflammatory effects of abalone intestine as byproducts from fishery manufacturing may suggest the possibility of high valuable utilization and application as a nutraceutical and therapeutic substance.