A new glycoprotein JGP-III2 was obtained from jellyfish. JGP-III2 is composed of 11.87% carbohydrate and 87.74% protein, which presents a molecular weight of 39.5 kDa. JGP-III2 is composed of eight types of monosaccharides: mannose, 2-amino-D-glucose, galactosamine, lactose, glucose, galactose, xylose, and fucose in a ratio of 6.88:5.13:5.19:70.78:1.47:2.09:6.59:1.85. The total amino acid content in JGP-III2 is 85.95%. Glycine is the major amino acid, followed by valine and glutamic acid. JGP-III2 presents N- and O-glycosidic bonds and is homologous to protein (gi|156215071) from Nematostella vectensis. The immune activity and immune mechanism of JGP-III2 were investigated using an immunocompromised mouse model. Compared with the control group, JGP-III2 significantly improved the spleen index, the thymus index, the phagocytic ability of the macrophages, serum hemolysin levels, and the number of antibody producing cells and delayed the allergic reaction in immunocompromised mice. The results showed that JGP-III2 could enhance the immune ability of these mice. Furthermore, JGP-III2 could promote the mRNA expression of Th1-type cytokines, inhibit the mRNA expression of Th2-type cytokines, and restore the “Th1/Th2 shift” found in the control group. JGP-III2 is considered to enhance the immune activity by regulating the Th1/Th2 balance.