Diabetes mellitus is a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia together with the disturbance of carbohydrate, fat, protein metabolism resulting from a defect of insulin secretion, insulin action or both which affects most of the people in both developed and developing countries. Apart from insulin therapy (mainly for type 1 diabetes mellitus), several synthetic drugs are available in the market to treat diabetes, but the treatment with synthetic drugs is costly and the chances of side effects are high. The present work aimed to compile the detailed information about the naturally-occurring alkaloids having an effect against diabetes and diabetes-related complications. A detailed literature survey was conducted to collect information. Different online scientific database such as PubMed, Scopus, and Web of Science were searched together with some relevant books. Since ancient times, plants and their derived products have been used to treat human ailments in various parts of the world where access to modern medicine is limited. About 800 species of medicinal plant have been reported for anti-diabetic effect. A wide range of active constituent derived from plants such as alkaloids, glycosides, terpenoids, steroids, flavonoids, anthocyanidins, resins and saponins have been found active against diabetes. Alkaloids are a class of naturally-occurring chemical compounds, derived from natural sources such as plants, animals, bacteria and fungi. They have a wide range of pharmacological activities such as anti-malarial, anti-asthmatic, anti-cancer, anti-hypertensive, oxytocic, CNS stimulant, muscle relaxant, anti-spasmodic, cholinomimetic, vasodilatory, anti-arrhythmic, analgesic, anti-bacterial and anti-hyperglycemic. The present paper reviews the effect of alkaloids against diabetes and diabetes-related complications such as neuropathy, diabetic ketoacidosis, kidney disease (nephropathy), cardiovascular disease (hypertension), hyperosmolar hyperglycemic nonketotic syndrome, stroke, gastroparesis and eye problems (cataract, keratopathy and retinopathy). Various alkaloids including berberine, boldine and sanguinarine were found potentially effective against different diabetic models. The present work concluded that there are many alkaloidal compounds present in nature which can be used to develop a new promising drug against diabetes and diabetes-related complications.