Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition characterized by elevated glucose levels followed by deficiency in insulin secretion. Metformin notably decreased the incidence of T2DM by 31% and it exerts its effects through various signaling pathways. Databases searched included PubMed, Google Scholar, and Scopus from 2000 to 2024. One of the primary mechanisms involves AMPK activation which causes reduced lipogenesis and improved fatty acid oxidation in the liver and muscles. Key molecules affected by metformin include acetyl-CoA carboxylase (ACC) and sterol regulatory element-binding protein 1c (SREBP-1c), both involved in lipid synthesis regulation. Aerobic exercise has also emerged as a crucial component in managing T2DM due to its improved effects on hyperglycemia and insulin sensitivity. Key signaling pathways affected in T2DM include the PI3K/Akt, AMP-activated protein kinase (AMPK), and MAPK/ERK pathways which play essential roles in regulating glucose homeostasis, glycogenesis, and insulin secretion. When comparing the mechanisms and efficacy of aerobic exercise and metformin, it becomes evident that aerobic exercise primarily enhances physical fitness and metabolic function, while metformin exerts its effects through biochemical pathways involving AMPK activation. Aerobic exercise and metformin are effective for managing T2DM, though they operate through different mechanisms. Regular aerobic exercise improves insulin sensitivity, enhances cardiovascular health, and promotes weight loss, while metformin primarily decreases hepatic gluconeogenesis and enhances insulin secretion. Understanding the intricate signaling pathways affected by metformin and aerobic exercise provides valuable insights into its mechanisms of action and clinical implications for treating diabetic patients effectively.