Background: According to the International Diabetes Federation, Egypt has one of the world's top ten highest concentrations of diabetics. This figure is anticipated to climb to 13.1million by 2032 from the current 7.5 million diabetics and 2.2 million pre-diabetic population in Egypt. Several transcription factors are coactivated by Peroxisome Proliferator-activated Receptor Gamma Coactivator 1 Alpha (PGC-1α), a transcriptional coactivator. Oxidative metabolism is one of its numerous biological impacts, and it affects ROS production and mitochondrial biogenesis. Mitochondrial dysfunction is seen in T2DM patients, who have fewer mitochondria in their skeletal muscles. Objective: To determine if PGC-1α gene polymorphism is correlated with T2DM. Methods: PubMed, Google Scholar, and Science Direct were searched using the following keywords: Type 2 Diabetes Mellitus, Peroxisome Proliferator-activated Receptor Gamma Coactivator 1 Alpha, and PGC-1α. The authors also screened references from the relevant literature, including all the identified studies and reviews, only the most recent or complete study was included, and in peer-reviewed articles between March 2001 and February 2021. Documents in a language apart from English have been excluded as sources for interpretation were not found. Papers apart from main scientific studies had been excluded: documents unavailable as total written text, conversation, conference abstract papers, and dissertations. Conclusion: PGC-1α has been implicated in the regulation of genetic pathways leading to homeostatic liver and muscle glucose use, mitochondrial biogenesis as well as insulin production.