BACKGROUND Rotheca myricoides (Hochst.) Steane & Mabb is a plant species used in traditional medicine for the management of diabetes in the lower eastern part of Kenya (Kitui, Machakos and Makueni Counties, Kenya) that is mainly inhabited by the Kamba community. OBJECTIVE This study investigated the antihyperglycaemic, antidyslipidemic and antihyperinsulinemic activity of the freeze-dried extracts of Rotheca myricoides (Hochst.) Steane & Mabb (RME) in an animal model of type 2 diabetes mellitus. METHODS Type 2 diabetes was induced by dietary manipulation for 56 days via (high fat- high fructose diet) and intraperitoneal administration of streptozocin (30 mg/kg). Forty freshly-weaned Sprague Dawley rats were randomly assigned into the negative control (high fat/high fructose diet), low dose test (50mg/kg RME, high dose test (100mg/kg RME and positive control (Pioglitazone, 20mg/kg) groups. Fasting blood glucose and body weight were measured at weekly intervals. Oral glucose tolerance tests were performed on days 28 and 56. Lipid profile, hepatic triglycerides, fasting serum insulin levels and serum uric acid were determined on day 56. RESULTS The RME possessed significant antihyperglycemic [FBG: 6.5 ± 0.11 mmol/l (negative control) vs. 4.62 ± 0.13 mmol/l (low dose test) vs. 5.25 ± 0.15 mmol/l in (high dose test) vs. 4.33 ± 0.09 mmol/l (positive control): p < 0.0001] and antihyperinsulinemic effects [1.84 ± 0.19 (negative control) vs. (0.69 ± 0.13 (low dose test) vs. (0.83 ± 0.17 (high dose test) vs. (0.69 ± 0.10 (positive control): F (3, 36) = 0.6421: p < 0.0001. The extracts also possessed significant antidyslipidemic effects [LDL levels: 3.52 ± 0.19 mmol/l (negative control) vs. 0.33 ± 0.14 mmol/l (low dose test) vs. 0.34 ± 0.20 mmol/l (high dose test) vs. 0.33 ± 0.01 mmol/l (positive control): p < 0.0001].RME significantly lowered plasma uric acid levels, as well as hepatic triglycerides and hepatic weights. Network pharmacology analysis indicated that the observed pharmacological effects are mediated via the modulation of Peroxisome proliferator-activated gamma receptor. CONCLUSIONS The freeze dried extracts of Rotheca myricoides possessed significant antihyperglycemic and antidyslidemic effects. In addition it lowered serum uric levels, as well as hepatic triglycerides and hepatic weight. These results appear to validate the traditional use of this plant species in the management of diabetes mellitus.