Metabolic syndrome is a complex of metabolic disorders characterized by oxidative stress which compromises cell functions and entails multiple organs pathologies. We investigated the therapeutic and protective potential of Adansonia digitata fruit -a potent antioxidant- in high sugar/high fat diet-simulated metabolic syndrome in Wistar rats. 42 male rats (140-200 g) were randomly divided into 7 groups. G1 was kept on standard laboratory diet (SLD) for all 9 weeks (negative control). 5 groups were fed high Sugar/high fat diet for 6 weeks then switched to SLD for another 3 weeks + oral treatment as follows: G2+ no treatment (positive control), G3-G5 + 200, 400 and 800 mg/kg/day aqueous A. digitata fruit respectively, G6 + 10 mg/kg/day Simvastatin. G7 + HS/HFD + 400 mg/kg/day A. digitata fruit simultaneously and was terminated at W6. Our results showed that G2-G6 develops dyslipidemia, hyperglycaemia, weight gain, elevated hepatic biomarkers, elevated creatinine and urea plus pathological derangements in the heart, liver and kidney tissues compared to negative control at W6. 200 mg/kg/day A. digitata fruit significantly ameliorated the induced dyslipidemia (P ≤ 0.001), hyperglycaemia (P ≤ 0.001) with a significant reduction in the Atherogenic Index of Plasma (P ≤ 0.000) after 3 weeks treatment. The fruit normalized the elevated hepatic biomarkers as well as creatinine and urea. A dose dependent partial reduction in lesion intensity was observed in the hepatic tissue while the heart and kidney showed mostly reversed to normal histology. The inflammatory infiltration was eliminated. Relevant results were observed for the two higher doses. The simultaneous treatment showed significant lower levels in all biomarkers investigated compared to positive control which could be interpreted as protective activity. A reduction of 4-11% in whole body weight was achieved. CONCLUSION: MetS was successfully simulated with a HS/HFD formula in male Wistar rats. Treatment with aqueous A. digitata fruit showed anti-Metabolic Syndrome potential reflected by weight loss, anti-inflammatory, hypolipidemic, hypoglycaemic, renal, hepatic and cardio-protective activities.