Hippophae rhamnoides L. polysaccharide (HRP) has antioxidant and immunomodulatory actions. It has been reported that HRP can reduce the release of reactive oxygen species (ROS). The objective of this study was to investigate the effects of HRP on immunomodulatory and antioxidant activity in intestinal porcine jejunum epithelial (IPEC-J2) cells. Effective conditions of HRP (0, 200, 400, 600, and 800 μg mL^-1) were evaluated by pretreatment of IPEC-J2 cells for 24 h. The results showed that pretreatment with 0–600 μg mL^-1 of HRP enhanced cell survival rate, while more than 600 μg mL^-1 posed a threat to IPEC-J2 cell viability and lowered cell survival rate (p < 0.05). In addition, results revealed that, compared with the control group, the treatment of IPEC-J2 cells with 200–600 μg mL^-1 of HRP for 24 h decreased ROS, malondialdehyde, protein carbonyl levels, and cell apoptosis. Meanwhile, the levels of superoxide dismutase, glutathione peroxidase, interleukin-1 beta, interleukin-2, interleukin-6, interleukin-8, tumour necrosis factor-alpha were elevated, and enhanced relative mRNA levels were also shown in the IPEC-J2 cells. Both the contents of immunoglobulin M, immunoglobulin A, and immunoglobulin G elevated with the increases of HRP concentration (200, 400, and 600 μg mL^-1), and an increase of catalase relative mRNA levels were also observed in IPEC-J2 cells. Data indicated that 600 μg mL^-1 of HRP had a potent protective effect on IPEC-J2 cells. Taken together, these results suggested that HRP was effective in regulating intestinal epithelial cells in piglets.