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Purpose: Despite readily available over-the-counter drugs, most herbal products are not scientifically validated for their safety profile. The study aimed to evaluate the safety profile of marketed anti-diabetic herbal medicines in Ghana. Design/Methodology/Approach: Four antidiabetic herbal medicines were purchased from herbal shops at Okaishie market in Accra. The mixtures were dried at 70oC in a water bath to obtain powdered extracts. A single dose of 5000mg/kg body weight of each extract was administered to 10 female Sprague Dawley rats once for the acute toxicity studies, and signs of toxicity were observed. Histopathological examination of essential organs was conducted after sacrificing the rats. P < 0.05 was considered statistically significant after multiple comparison tests. Findings: No mortality or adverse side effects were recorded. The rats' normal growth, food, and water consumption were observed during the study period. No significant biochemical or haematological differences were observed, and no significant histological alterations were observed in the tissues studied. Research Limitation: This study used a specific batch of screened antidiabetic herbal medicines, and the results cannot be generalised to all batches of these herbal medicines. Practical Implication: It will help the Food and Drugs Authority, Ghana Standard Authority, Ministry of Health, and Ghana Health Service to intensify their surveillance of these antidiabetic herbal medicines. Social Implication: Safety evaluation of herbal medicines is vital in protecting society from serious adverse health effects from harmful herbal products. Originality/Value: The study employs laboratory animals to assess these herbal medicines for safety evaluations. Rats have almost the same physiology and anatomy as humans. [ABSTRACT FROM AUTHOR]