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Insulin resistance is a primary risk factor for developing diabetes. However, diabetes drugs generally focus on regulating and lowering patients’ blood glucose levels. In recent years, diverse materials have been evaluated to improve insulin resistance and hinder the development of diabetes. Momordica charantia extract (MCE) and lactic acid bacteria (LAB) have been considered as potential therapeutic agents against insulin resistance and hyperglycemia. In a streptozotocin-induced type 1 diabetes animal model, treatment with MCE and LAB had no effect on hyperglycemia. To evaluate the effect of MCE and LAB on insulin resistance, we chose a high-fat diet-induced insulin resistance model and co-administered MCE and Lactobacillus Acidophilus CBT-LA1, Lactiplantibacillus plantarum CBT-LP3, or Lacticaseibacillus rhamnosus CBT-LR5. MCE with CBT-LA1 or CBT-LP3 improved insulin resistance and hepatosteatosis. However, the effect of MCE and MCE with CBT-LR5 was weaker than the effect of MCE with CBT-LA1 or CBT-LP3. Momordica charantia induced insulin secretion from RIN-m5F in a dose-dependent manner. Interestingly, CBT-LA1 and CBT-LP3 enhanced the insulin secretion of MCE. These results suggest that the co-administration of MCE and a specific LAB is one approach for overcoming insulin resistance and hyperglycemia.