<p>The biological rhythm of the human body runs in a 24-h cycle in which it undergoes various interactions with exogenous factors, resulting in variations of endogenous components as well. Exogenous factors like exposure to artificial light, shift work, jet lag, sleep desynchrony, irregular food intake, disturbed gut health, and endogenous factors like family history and genetics are the primary regulators of the master clock of the body. The Master Clock of the human body refers to the Suprachiasmatic Nucleus (SCN) present in the hypothalamic region of the human brain; it in turn, regulates the other peripheral clocks of the body. The mainstream Circadian Locomotor Output Cycles Kaput (CL) genes that regulate the molecular feedback in circadian regulation include Period Circadian Regulator (PER), Cryptochrome Circadian Regulator (CRY), and Brain and Muscle Arnt-like protein-1 (BMAL1), which regulate the Clock Controlled genes (CCGs). Any desynchrony in the central or peripheral clock has been well associated with impaired insulin sensitivity, which is one of the hallmarks of type 2 diabetes mellitus, and known as insulin resistance. The Clock Controlled Genes (CCGs) undergo genetic alterations leading to Single Nucleotide Polymorphisms (SNPs) due to interaction with epigenetic factors, resulting in detrimental or protective effects on the pathogenesis of type 2 diabetes. This review focuses primarily on circadian rhythm desynchrony and how it relates to insulin resistance and type 2 diabetes mellitus (T2DM) with a brief introduction to the T2DM associated Circadian gene polymorphisms.</p>