Endoplasmic reticulum (ER) is a cellular compartment responsible for biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. ER stress plays a role in the pathogenesis of diabetes and is associated with pancreatic ${eta}$-cell damage. The aim of this study was to examine the effect of KIOM-79, a mixture of plant extracts, on streptozotocin (STZ)-induced ER stress in pancreatic RINm5F ${eta}$-cells. STZ induced characteristics of ER stress; the release of $Ca^{2+}$ from ER, increased ER staining, induction of glucose-regulated protein-78, phosphorylation of PKR-like ER kinase, and eukaryotic initiation factor-$2{alpha}$, as well as cleavage of activating transcription factor-6, whereas KIOM-79 inhibited these changes. Moreover, KIOM-79 inhibited STZ-induced apoptotic cell death. STZ induced CCAAT/enhancer-binding protein-homologous protein (CHOP) and cleavage of caspase 12, which are ER stress-induced apoptosis regulatory proteins; however, KIOM-79 suppressed these effects. KIOM-79 suppressed apoptosis induced by STZ treatment in CHOP siRNA-transfected cells. Furthermore, KIOM-79 restored cell viability decreased by STZ treatment via ER-stressed apoptosis. The pancreatic ${eta}$-cells damaged by STZ had decreased levels of insulin, and KIOM-79 restored the levels. Taken together, these results suggest that KIOM-79 had cytoprotective effects against STZ-induced apoptosis by interrupting the ER stress pathway.