Objectives The management of diabetes is considered a global problem, and a cure is yet to be discovered. This study investigated the modulatory effect of Kigelia africana fruit on oxidative stress and hyperlipidaemic biomarkers in STZinduced diabetic rats, profiled phytoconstituents using GC-TOF-MS and evaluated antidiabetic effects on 3T3 L1 adipocytes. Methods Thirty male Wistar rats (120-150 g) were divided into six groups (n = 5). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) and treated with 100, 200 and 400 of hexane fraction of KA for 28 days. Immunohistochemical evaluation was carried out using avidin-biotin immunoperoxidase (ABI) method. Catalase and SOD activities as well as the levels of total protein, albumin, bilirubin, triglyceride, cholesterol, and high-density lipoprotein were measured. Key findings The expressions of oxidative stress and hyperlipidaemic biomarkers alongside fasting blood glucose concentrations were remarkedly decreased in KAtreated diabetic rats. Moreover, there was a significant increase in endocrine cell distribution, area covered with increase in b-cell mass, composition and morphology of KA-treated animals. Additionally, there was constant up-regulation in 3T3 L1 adipocytes due to the presence of phytoconstituents. Conclusion Kigelia africana fruit can act as a modulatory agent due to its ameliorative effects against oxidative stress. Highlights âą Kigelia africana fruit increases b-cell mass within the pancreas of diabetic rats âą K. africana fruit consists of 376 metabolites and chemical compounds âą K. africana fruit exhibited an up-regulation glucose uptake in 3T3 L1 adipocytes âą K. africana fruit can maintain or reverse biochemical integrity of diabetic rats Oladapo F. Fagbohun et al. Modulatory effects of K. africana fruits