This study investigated the hypoglycemic, antihyperlipidemic, and renoprotective potentials of Dennettia tripetala (DT) in a rat model of diabetes. The hypoglycemic activity in crude methanol seed extract of DT (CMEDT) and methanol seed fraction of DT (MFDT) measured by glucose oxidase method was increased by 47.37% and 28.72%, respectively, after 8 hours of administration. After 10 days of treatment, CMEDT and MFDT gave a good glycemic control with the highest percentage reduction of 75.82% and 71.34% in glucose level, respectively, which is closely compared with 79.91% in glibenclamide. Using the enzymatic assay and Friedewald's equation, there was a significant reduction in serum level of total cholesterol (TC), triglyceride (TG), very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) and a significant increase in high-density lipoprotein (HDL) (p < 0.05) following treatment with CMEDT and MFDT, when compared with the untreated group, although results varied in dosed groups, with high dose of MFDT showing a better lipid-lowering activity. High dose of MFDT improved lipid metabolism and increased percentage protection against atherogenesis by 44%. However, neither CMEDT nor MFDT ameliorated the renal biochemical alteration in urea and creatinine. Thus, the study demonstrates hypoglycemic and antihyperlipidemic potentials of DT seed in diabetes.