This experiment discussed the immunomodulatory effect of MMO in vitro, which used Meretrix meretrix oligopeptides (MMO) as raw material and RAW264.7 cells as experimental models. The research set up control group, positive medicine group (lipopolysaccharides, LPS), low concentration MMO group, medium concentration MMO group, and high concentration MMO group. Cell activity was detected by methyl thiazolyltetrazolium (MTT) colorimetric method, cell cycle was detected by flow cytometry, and cell morphology change was observed by hematoxylin-eosin staining (H.E) and cell phagocytosis ability was detected by neutral red phagocytic experiment. And immunofluorescence labeling was used to observe the expression of iNOS in cells. The contents of nitric oxide (NO), interleukin-6 (IL-6), interleukin-1β (IL-1β) in cell supernatant were detected by nitrate reductase analysis and enzyme-linked immunosorbent assay (ELISA). The results showed that MMO group exhibited increased proliferation and differentiation of RAW264.7 cells. When the concentration of MMO was 250 μg/mL, it obviously enhanced the phagocytosis capacity, increased the G1/G0 phase and G2/M phase cells in the cell cycle, induced NO release of iNOS, and promoted the secretion effect of IL-6 and IL-1β. All the phenomena were similar to LPS for RAW264.7 cells. Therefore, it is proved that MMO has the effect of promoting the activation of RAW264.7 cells and the potential of enhancing the non-specific immunity.