This study aimed to investigate the effect of Lactiplantibacillus plantarum SCS4 in alleviating oxidative stress in the pancreatic tissue of hyperglycemic mice. A total of 90 six-week-old specific pathogen-free male Kunming mice were randomly divided into six groups [normal group (NG), blank control group (MG), phosphate-buffered saline (PBS) control group (CG), SCS4 first control group (DT1), SCS4 second control group (DT2), and SCS4 third control group (DT3)]. Except the NG group, in the other five groups, streptozotocin (STZ) was intraperitoneally injected for five consecutive days to establish a hyperglycemia model; the concentration of STZ was 50 mg/kg (bw). After successful modeling, DT1, DT2, and DT3 mice were administered 0.2 ml of L. plantarum SCS4 bacterial solution (10 10 colony forming unit/ml), the cellular content of L. plantarum SCS4, and the inactivated cellular content of L. plantarum SCS4, respectively. Furthermore, 0.2 ml of PBS was given to mice in the CG group for control. The levels of insulin (INS), reactive oxygen species (ROS), malondialdehyde (MDA), and antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured by enzyme-linked immunosorbent assay, and the morphology of the pancreas was observed. The results showed that after 10 weeks of gavage treatment, the level of INS in the DT3 group significantly increased to 6.36 mIU/L compared with that in the MG group (p < .05). Meanwhile, the levels of ROS and MDA of DT3 returned to normal levels of 291.07 IU/ml and 4.29 mnol/L, respectively. The activities of various antioxidant enzymes increased. The levels of SOD, CAT, and GPx in DT3 were the closest to the levels in NG. In addition, the pathological sections showed that the degree of pancreatic tissue lesions was relatively more severe in the MG group than in the NG group. The degree of pancreatic tissue lesions was relatively less severe in the DT2 group than in the MG group, and no significant lesion was seen in the DT3 group. Our results indicated that the inactivated bacterial content of L. planetarium SCS4 was more effective in improving oxidative stress in the pancreas of hyperglycemic mice.