Type-2 diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia that arises by insufficient insulin secretion or action. DM is a non-communicable disease that has reached epidemic proportions; up to 2017, around 425 million people were living with diagnosed DM, and this number is expected to increase by 48% in 2045. The first line of treatment against DM consists of hypoglycemic drugs, such as acarbose and metformin. However, people from low- and middle-income countries often struggle to access these medications. This turns them to use either only medicinal plants or in combination with conventional treatments. Thus, this chapter aims to comprehensively review the current literature (2010–2020) regarding the potential pharmaceutical properties of plant alkaloids in the treatment/prevention of diabetes mellitus and its comorbidities.