Abstract: This study aimed to investigate the immune-regulating mechanism of the ginseng sea buckthorn complex (GSC) using network pharmacology, molecular docking, cellular experiments, and animal experiments. Network pharmacology was applied to predict potential immune-regulating pathways and key targets of GSC. Molecular docking was performed to assess the binding properties between GSC components and these key targets. Cellular and animal experiments were designed to verify the immune-regulating effect of GSC. Results showed that network pharmacology predicted GSC might regulate immune function by acting on signaling pathways such as lipid and atherosclerosis and MAPK signaling pathway, as well as key targets including tumor necrosis factor (TNF). Molecular docking results indicated that GSC components exhibited good binding properties with the key target TNF, with all binding energies below −6.00 kcal/mol. Cellular experiments demonstrated that GSC increased TNF-α secretion in RAW264.7 macrophages: Low, medium, and high doses elevated TNF-α secretion from 1201.96 pg/mL to 1908.63 pg/mL (P<0.001), 1859.04 pg/mL (P<0.001), and 1737.38 pg/mL (P<0.001), respectively. In animal experiments, GSC showed a significant immune-enhancing effect: The spleen index was increased to 0.3273% (P<0.05), the optical density difference was raised to 0.06 (P<0.001), the toe thickness difference was increased to 0.58 mm (P<0.001), and the half-hemolysis value was enhanced to 106.10 (P<0.01). In conclusion, GSC may exert immune-regulating effects by modulating signaling pathways such as lipid and atherosclerosis, MAPK signaling pathway to affect immune cell activity, while regulating TNF-α concentration.