The majority of diabetes-related conditions occur as a result of abnormal chemical reactions in hyperglycemia that alter normal metabolic processes. Hyperglycemia is a key process in unregulated Ca2+ leakage, inflammation, and immune-system disorders, and it can lead to a number of short- and long-term health complications, including diabetic cardiomyopathy. Ryanodine receptors (RyRs) play a key role in excitation-contraction-coupling during heart contractions including rhythmic contraction and relaxation of the heart-and are important for controlling cardiac fibroblast function, are expressed in immune cells, and are involved in important mechanisms underlying diabetes-related complications. However, little is known regarding the mechanistic relationship between RyRs and immunity-related molecules in diabetes, as well as the mechanisms mediating complex communication among cardiomyocytes, fibroblasts, and immune cells. This review highlights new findings on complex cellular communications in the pathogenesis and progression of diabetic cardiomyopathy. Furthermore, we discuss potential therapeutic applications targeting RyRs and immunity-related molecules in diabetic complications.