<p>Diabetes mellitus, a global health threat, is associated with living standards, age, genetics of the host, and other factors. Diabetes has three major types, Type 1 diabetes, Type 2 diabetes, and Gestational diabetes. Out of these, type 2 diabetes (T2D) is the most prevalent type. Understanding the pathophysiology of T2D is challenging since it requires a knowledge of the intricate relationships between glucose metabolism, insulin secretion, sensitivity, and glucose effectiveness. The human gut microbiome, a complex assembly of microorganisms including bacteria, viruses, and other microbes, has drawn much attention recently due to its association with T2D. Patients with T2D exhibit altered microbial composition and diversity, along with dysbiosis in the gut microbiome. Glucose-lowering drugs used for treatment purposes, like acarbose and metformin, are related to microbiome dysbiosis. These glucose-lowering drugs also affect the metabolic pathways and functions in T2D patients including short-chain acids (SCFAs) synthesis, an important metabolic player in diabetes linked to the gut microbiome. Therefore, to improve T2D treatment and management, the gut microbiome becomes an important target. However, this remains challenging and necessitates a comprehensive understanding of the mechanism of gut microbes and their role in disease onset. Clinical trials are being conducted to study the effects of gut microbiome on T2D progression and the effect of glucose-lowering drugs on gut microbiome composition and diversity. This review explores the relationships between gut microbiome and T2D, focusing on how glucose-lowering drugs impact the gut microbiome of T2D patients. It also highlights the possible treatment considerations along with the challenges.</p>