The increase in blood glucose causes a myriad of pathways and molecular components to malfunction, leading to diabetes. Diabetes affects each organ differently by activating distinct pathways. It has an impact on the liver, pancreas, kidney (nephropathy), eyes (retinopathy), and nervous system (neuropathy). Understanding the effects of diabetes on each organ is the first step in developing a sustained treatment for the disease. Among the many cellular molecules impacted by diabetes is Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), a complex Ca²⁺/calmodulin-activated serine/threonine-protein kinase. When intracellular [Ca²⁺] rises, it binds to calmodulin (CaM) to produce Ca²⁺/CaM, which activates CaMKIIs. This factor is involved in the pancreas, liver, heart, muscles, and various organs. Thus, Understanding CaMKII action in each organ is critical for gaining a complete picture of diabetic complications. Therefore, this review covers CaMKII’s functions in many organs and how it affects and has been affected by diabetes.