Diabetes mellitus is one of the most common non communicable diseases around the world and is responsible for many deaths resulting from some of its serious complications. Senna occidentalis Linn. is extensively being used in folklore medicine to cure and/or manage many disease conditions, although its adequate validation as therapeutic (specifically anti-diabetic and hepatoprotective) effects has not been established. The aim of this study is to determine the effects of Senna occidentalis leaf supplement on blood glucose level, liver enzymes and total protein in alloxan-induced diabetic wistar rats. Diabetes was induced by single intraperitoneal injection of alloxan (150 mg/kg). Thereafter the rats were fed with Senna occidentalis leaf supplement at doses of 12.5%, 25% and 50% .Also Glibenclamide was used as a standard drug (2 mg/kg) as positive control and diabetic control received distilled water as negative control. Blood glucose levels were measured at day 0, 4, 8, 12 and 16. The liver enzymes and total protein were also determined using the serum and histopathological studies of the pancreas and liver were conducted. Quantitative phytochemical screening revealed that the supplement has high amount of phytoconstitutuents like total phenols, flavonoids, tannins, saponins and alkaloids, which have a percentage composition of 20%, 10.80%, 15%, 0.55% and 7.20%, respectively. Blood glucose levels of all animals treated with the supplement were reduced significantly (p<0.05) by about 82.13%, 88.36 and 81.78% respectively when compared with that of the untreated diabetic control group. There was also an increase in the total protein (p< 0.05) to 90.98 ± 6.02, 73.72 ± 3.02 and 92.23 ± 4.01, respectively in comparison to that of the untreated diabetic group having 69.04 ± 3.59; and hepatotoxicity due to the observed increase in the activities of all the liver enzymes as well as hepatocellular necrosis, sinusoidal congestion and hemorrhage as revealed in the histopathological studies of the liver. This study shows that S. occidentalis leaf supplement has potent hypoglycemic effect due to its high content of active principles that possess strong and potent insulinomimetic and β-cell regenerating potential as depicted by the histopathological studies of the pancreatic tissue, even though, some cytotoxic agents like the cytotoxic saponins may be present in the supplement which is capable of causing damage to both pancreas and liver. These findings prove its use in traditional medicine for the treatment of diabetes but with caution due to its probable potential to induce hepatotoxicity.