This research was performed to observe the effects of glutamine (Gln), Isomaltooligosaccharide (IMO) and their interaction on serum immune indexes and antioxidant capacity of weaned piglets. Eighty-one healthy "Duroc×Landrace×Yorkshire" crossbred piglets weaned at 28 days of age with similar body weight of (7.54±0.62) kg was randomly distributed into 9 groups with 3 replicates per group and 3 piglets per replicate by factorial design with two factors and three levels. Piglets were fed the diets supplemented with 0 g/kg both Gln and IMO (control group), 0 g/kg Gln and 6 g/kg IMO (groupⅠ), 0 g/kg Gln and 10 g/kg IMO (groupⅡ), 10 g/kg Gln and 0 g/kg IMO (group Ⅲ), 10 g/kg Gln and 6 g/kg IMO (group Ⅳ), 10 g/kg Gln and 10 g/kg IMO (group Ⅴ), 15 g/kg Gln and 0 g/kg IMO (group Ⅵ), 15 g/kg Gln and 6 g/kg IMO (group Ⅶ), 15 g/kg Gln and 10 g/kg IMO (group Ⅷ), respectively. The pretest lasted for 7 days, and the experiment lasted for 21 days. The results showed as follows:1) diets supplemented with 15 g/kg Gln significantly increased the content of immunoglobulin M (IgM) in serum of weaned piglets (P<0.05), and had no significant effects on the contents of immunoglobulin A (IgA) and immunoglobulin G (IgG) in serum (P>0.05). Diets supplemented with IMO had no significant effects on the contents of IgA, IgG and IgM in serum (P>0.05). The interaction of Gln and IMO had significant effect on the content of IgM in serum (P<0.05), especially in groups Ⅳ and Ⅶ. 2) Diets supplemented with Gln significantly decreased the content of malondialdehyde (MDA) in serum of weaned piglets (P<0.05), and had no significant effects on the activity of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in serum (P>0.05). Compared with the control group, diet supplemented with 6 g/kg IMO significantly decreased the content of MDA in serum (P<0.05), and had no significant effects on the activity of SOD and T-AOC in serum (P>0.05). The interaction of Gln and IMO had significant effect on the content of MDA in serum (P<0.05), and had an increasing tendency for the activity of SOD in serum. Taken together, the effect of group Ⅷ was the best. It is concluded that diets supplement with 15 g/kg Gln and 6 g/kg IMO can improve immune function and antioxidant capacity of weaned piglets.