Background: Diabetes mellitus is a metabolic syndrome exaggerated by stress conditions. Endoplasmic reticulum stress (ERS) impairs the insulin signaling pathway making the diabetic conditions worsen. Pharmacological agents are supplied externally to overcome this malfunction. Ginsenosides from Panax ginseng C.A Meyer possesses many pharmacological properties and are used for the treatment of diabetes. Objective: To investigate the effects of the Rk 1 +Rg 5 complex on the amelioration of insulin resistance in 3T3-L1 cells under endoplasmic reticulum stress conditions. Materials and Methods: Heat-processed ginseng extracts are found to contain many pharmacologically active ginsenosides. Among them Rk 1 +Rg 5 is found to be present in higher concentrations than the other minor ginsenosides. The Rk 1 +Rg 5 complex was tested for its effect in the 3T3-L1 insulin-resistant model and subjected to the MTT assay, glucose oxidase assay and gene expression studies using RT-PCR and real-time PCR under endoplasmic reticulum stress conditions. Results: Rk 1 +Rg 5 treatment is found to increase the glucose uptake into the cells when compared to that of a positive control (tunicamycin treatment group, TM). Further we have analyzed the role at gene expression level. The Rk 1 +Rg 5 complex was found to show an effect on the IGF 2R receptor, CHOP-10, and C/EBP gene at a particular treated concentration (50 μM). Moreover, stress condition (about 50% decreases) was overcome by the ginsenoside treatments at 50 μM. Conclusion: The present results showed that under endoplasmic reticulum stress conditions Rk 1 +Rg 5 complex exhibits a potential protective role in insulin-resistant 3T3-L1 cells.