Diabetes mellitus (DM) is a critical health issue prevailing in nearly half a billion people worldwide. It is one of the most threatening metabolic diseases. Type 2 DM is caused due to insulin resistance and accounts for 90% of diabetes cases. If it remains untreated, it can lead to major frightening complications and can cause death, which ultimately threatens humankind.Various oral hypoglycaemic drugs are available today, acting on different targets by adopting different pathways. However, the α-glucosidase inhibitors proved to be a novel and effective strategy to manage T2DM. These inhibitors alleviate postprandial glycemia by aiming to inhibit intestinal α-glucosidase competitively and reversibly, thus delaying carbohydrate digestion and turning down the rate of glucose absorption. Plenty of α-glucosidase inhibitors have been discovered from synthetic routes as well as from natural sources, including plants, fungi, and bacteria.This article comprises the natural and synthetic α-glucosidase discovered from 2016 to 2021 and can be utilized to discover novel α-glucosidase inhibitors. This review is an endeavor to highlight the progress in the discovery and development of α-glucosidase inhibitors, which could provide an overview to the medicinal chemists for the development of clinically viable drugs using this information.