Insulin-sensitizing antihyperglycemic drugs are a class of medications used in the management of diabetes mellitus, particularly type 2 diabetes, by improving the body’s response to insulin. One prominent group within this category is the thiazolidinediones (TZDs), which include drugs like pioglitazone and rosiglitazone. These medications act primarily by activating peroxisome proliferator-activated receptor gamma (PPARγ) receptors, which play a key role in regulating glucose and lipid metabolism. By enhancing insulin sensitivity in peripheral tissues such as muscle, adipose tissue, and liver, TZDs help lower blood glucose levels. However, their use has been associated with adverse effects, including weight gain, edema, and an increased risk of heart failure. Another class of insulin-sensitizing agents is the biguanides, such as metformin, which primarily work by reducing hepatic glucose production and improving insulin sensitivity in the liver. Metformin is widely prescribed as a first-line therapy due to its efficacy, safety profile, and additional benefits such as weight neutrality or modest weight loss. Insulin-sensitizing antihyperglycemic drugs are often used in combination with other diabetes medications to achieve optimal glycemic control, tailored to individual patient needs and considerations regarding potential side effects and comorbidities.