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Background: Many studies have reported the beneficial health properties of Garcinia kola (G. kola) seed from Ivory Coast. This study aimed to investigate the toxicity, anti-hyperlipidemic, and anti-hyperglycemic effect of aqueous extract of G. kola (AEGk) seed in rats subjected to the High Fat and Sucrose Diet (HFSD).Methods: Acute toxicity study was performed according to Organisation for Economic Co-operation and Development (OECD) Guidelines 423. In this study, AEGk was administered starting at 2000 mg/kg and followed by 4000 mg/kg. Rats were observed for toxic signs at 24 h and the next 14 days. For the AEGk effect on hyperlipidemia, hyperglycemia and liver and kidney biochemical markers, animals were divided into five groups. Group I (Control) was fed with a normal diet; Group II, III, IV and V were fed with HFDS and received respectively, 0,9% NaCl, 10 mg/kg statin, and 600 or 1000 mg/kg AEGk daily for four weeks. Finally, histological assessment of liver, kidney and adipose tissue was undertaken.Results: AEGk at single dose of 4000 mg/kg revealed no lethal effects. Treatment with AEGk significantly decreased hyperlipidemia (p<0.05), hyperglycemia and the relative weight of adipose tissue (p<0.001 for 1000 mg/kg). Histologically, fat deposits in the liver and kidney damage decreased.Conclusion: Overall, AEGk was relatively safe in rats at a single dose except for some transient disturbances (4000 mg/kg) and showed some potential in the management of cardiometabolic diseases.