Nereis virens (NV) is widely used as a high-quality feed for shrimp aquaculture and is also consumed for both medicinal and dietary purposes in China, Taiwan, and Southeast Asia. It is traditionally regarded to strengthen the spleen and stomach, tonify blood, promote diuresis to alleviate swelling, and reduce internal heat, thereby serving as a nourishing material. As an annelid, NV is also an important candidate for the development of marine-derived nutraceuticals. Previous studies have indicated that the serine proteases extracted from NV can inhibit the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT; PKB)/mechanistic target of rapamycin (mTOR) signaling pathway, which is associated with cell proliferation and inflammatory responses. Exercise-induced fatigue is commonly accompanied by inflammation, while subsequent recovery requires stimulation of muscle tissue repair and regeneration, which is closely related to the PI3K/AKT/mTOR pathway. This study will extend the collaboration established in the 2025 TEEP project with the Faculty of Fisheries at Kasetsart University (KU), in alignment with Taiwan’s Six Core Strategic Industries initiative on “Precision Health” and the “Biomedical Industry” sector of the 5+2 Industrial Innovation Program. An in vitro model using RAW 264.7 macrophages will be employed to simulate exercise-induced fatigue and recovery through different stimulatory conditions and treatment schedules, to investigate the regulatory effects of NV-derived bioactive peptides (NVP) on exercise fatigue.