Background: Tephrosia bracteolata Guill. & Perr. (Leguminosae-Papilionoideae) is a traditional Nigerian medicinal plant used for the treatment of whitlow, toothache, wounds, and diabetes. Aim: This study investigated the biochemical and histopathological effects of the ethanol extract of T. bracteolata leaves (EETB) and its fractions on alloxan-induced diabetic rats. Methods: EETB was fractionated successively with n-hexane, chloroform, ethyl acetate, methanol, and water to yield the respective fractions (nHF, CF, EAF, MF, and AF). The antidiabetic activities of EETB and its fractions at 250 and 500 mg/kg body weight (groups 4–15) were investigated in comparison to the normal control (group 1), the diabetic control (group 2), and the standard (150 mg/kg b.w. metformin, group 3) on alloxan-induced diabetic Wistar rats (200–220 g) for 28 days. Alterations in some biochemical parameters and histopathology of major organs were assessed. Results: Induction of diabetes triggered significant (p < 0.05) alterations in biochemical indices of the diabetic control relative to the normal control. Following treatments, EAF recorded the most potent effect by restoring altered biochemical parameters examined as indices of diabetic complications. Histopathological examination indicated a rapid regeneration of beta cells, hepatocytes, and nephrotic cells necrotized by alloxan, with EAF producing the best histo-architecture relative to EETB and other fractions. Conclusions: EAF indicated the most potent antidiabetic effect at the doses investigated, as it reversed complications associated with diabetes in Wistar rats, thus suggesting its potential for future development of potent antidiabetic drugs. Further studies on the characterization of the bioactive principles in EAF are underway. [ABSTRACT FROM AUTHOR]