The preparation process of Cryptotympana atrata peptide (CA-peptide) was optimized, and the immunomodulatory activities of CA-peptide and C. atrata protein (CA-protein) were compared. The optimal preparation conditions were determined as follows: 4% (m/m) alkaline proteinase 37071, 4% (m/m) trypsin, 5% (m/m) substrate, an initial pH of 10.5, and an enzymolysis temperature of 50 ℃. Enzymolysis was carried out separately with each protease for 1.5 h. Animal experiments showed that the related indices in immunocompromised mice induced by cyclophosphamide were improved to varying degrees by CA-peptide and CA-protein. At the same dose, the spleen index and proliferation rate of splenic lymphocytes in the CA-peptide group (2.40 mg/g and 51.07%, respectively) were significantly (P<0.05) higher than those in the CA-protein group. The serum immunoglobulin G, immunoglobulin A, immunoglobulin M, tumor necrosis factor-α, interleukin-4, and interleukin-10 levels in the CA-peptide group (701.67, 299.19, 239.88, 20.11, 33.86, and 71.15 ng/L, respectively) were significantly (P<0.05) higher than those in the CA-protein group. The thymus index and serum interferon-γ level in the CA-peptide group (1.36 mg/g and 36.26 ng/L, respectively) were significantly (P<0.05) lower than those in the CA-protein group. There was no significant difference in natural killer cell activity and serum interleukin-2 level between the CA-peptide and CA-protein groups (P>0.05). In conclusion, the enzymatic hydrolysis process has a profound impact on the immunomodulatory activity of CA-protein. Collectively, CA-peptide, exhibited stronger improvement effects on various immune indices compared with CA-protein.