Natural remedies have been used for decades to treat a variety of diseases. Diabetes mellitus (DM) is still one of the most common chronic diseases that cause death. Aside from its complex pathophysiology, it has been shown to be widespread in both developed and developing countries. The current pharmacological treatment has contributed to a significant reduction in disease occurrence. However, the economic burden and various pharmacological and non-pharmacological side effects associated with them, have necessitated the development of alternative naturally-derived treatment options. This review focuses on how safer, more effective, and less expensive treatments can help reduce diabetes-linked mortality rates. Furthermore, a wide range of medicinal plants with varying α-glucosidase and α-amylase inhibitory activity and improved IC50 and LD50 values evaluated in-vivo and in-vitro have been discussed. This review can help open new treatment paths for diabetes mellitus through new plant-derived medicines.