Marine-derived bioactive peptides are widely studied and used as functional foods. The aim of this study was to investigate the effects of low molecular-weight (Mw) peptides (150 Da < Mw < 1 kDa) from Nibea japonica muscles, referred to as Nibea japonica peptides (NJP), on the immune function of mice immunosuppressed with cyclophosphamide (CTX). The results showed that NJP significantly increased the splenic and thymic indices and alleviated the morpho-pathological characteristics of immune organs exposed to CTX. NJP enhanced phagocytosis by peritoneal macrophages and significantly increased proliferation of T lymphocytes activated with concanavalin A (Con A). NJP not only significantly promoted cytokine secretion, including interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), but also increased the levels of immunoglobulin (Ig) A, IgG and IgM in a dose-dependent manner, indicating that NJP can enhance both cellular and humoral immunity. Furthermore, we found that NJP could attenuate CTX-induced oxidative stress in multiple organs, suggesting that NJP may play a role in immune regulation by strengthening the body's antioxidant capacity. Therefore, NJP could be used as a natural immunomodulator in the functional food industry.