Objective: To explore the immunomodulatory effects of low-molecular-weight oyster peptides (LOPs) on short-term immunosuppressed mice. Method: One hundred and twenty male KM mice were randomly divided into control， cyclophosphamide model， whey protein and low-， medium- and high-dose LOPs groups according to their body mass. In the first three days of the experiment， the control group was injected intraperitoneally with saline 10 mL/kg bw per day， and the rest of the groups were injected intraperitoneally with an equal volume of cyclophosphamide 80 mg/kg bw per day to establish a short-term immunosuppressed mice model. Subsequently， 0.4 g/kg bw of whey protein was given by oral gavage to whey protein group， 0.2， 0.4， and 0.8 g/kg bw of LOPs were given by oral gavage to low， medium and high dose groups， respectively， and an equal volume of distilled water was given by oral gavage to control and model group， and body mass， immune organ mass and its histomorphology， serum lysozyme， cytokines and immunoglobulins were measured after 27 d of gavage. Result: Compared with the model group， the LOPs group helped repair damage to the morphological structures of spleen and thymus tissues， enhanced serum hemolysin levels， and increased interleukin-2， gamma-interferon， and immunoglobulin mass concentrations in mice. Conclusion: LOPs have immunomodulatory effects on cyclophosphamide of short-term immunosuppressed mice and have potential application as a base for special medical use formulae.