The effect of KIOM-4, a combination of four plant extracts was assessed on streptozotocin (STZ) treated rat insulinoma (RIN5mF) cells in vitro. KIOM-4 scavenged the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and intracellular reactive oxygen species (ROS) induced by STZ. KIOM-4 prevented the STZ-induced DNA damage, which is detected using comet as say, Western blot and lipid peroxidation assays. KIOM-4 inhibited the STZ induced apoptosis, therefore protecting from cell death. Additionally, KIOM-4 induced the activation of catalase and extracellular regulated kinase(ERK). These results suggest that KIOM-4 protects RINm5F cells via radical scavenging activity, the activation of catalase and ERK against STZ induced oxidative stress.