Mice lacking a functional leptin receptor (db/db mice) exhibit severe metabolic disease associated with marked hyperglycaemia, obesity, hypertriglyceridaemia, and fatty liver. These deleterious metabolic phenotypes are robust and difficult to correct; therefore, db/db mice represent an excellent model for testing experimental drugs. Herein, we show that the small molecule mitochondrial uncoupler BAM15 completely normalised hyperglycaemia and glucose tolerance in male db/db mice in a dose-dependent manner. BAM15 treatment also markedly improved liver and serum triglyceride levels. BAM15 increased energy expenditure leading to decreased body weight while preserving body composition including conserving skeletal muscle mass. The beneficial metabolic and weight loss effects of BAM15 were not due to decreased food intake. BAM15 treatment improved glucose homeostasis to a greater extent than two positive control groups including calorie restriction and the mitochondrial uncoupler niclosamide. BAM15-mediated improvements in glucose control were associated with decreased glucagon levels and decreased expression of enzymes involved in hepatic gluconeogenesis. In summary, BAM15 has strong glucose-lowering and anti-hepatosteatotic effects in db/db mice that support the further development of BAM15 and related molecules as pharmacotherapies for obesity-related diabetes.