From a health standpoint, fluoride (F) is a vital element for humans. It had harmful effects on numerous organs when consumed in high dosages. Fluoride poisoning has been linked to liver damage. The purpose of this study was to see how sodium fluoride (Naf) affected liver function and the glycemic index in adult male albino rats. Fourteen (14) adult male Wistar albino rats were randomly and evenly divided into two groups and given the following treatments for thirty (30) days: G1 Group (Control group), were given distilled water and fed a balanced diet, G2 rats were administered water that contained 100 ppm Naf. The animals were fasted for 8-12 hours before being anesthetized and blood samples were taken by heart puncture technique at zero day (zero time) and (30) day. The following parameters were measured using the serum. The glycemic index contains (glucose, insulin, and insulin resistance), as well as liver function tests such as serum activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT), as well as direct, indirect and total bilirubin concentration. The livers and pancreas were quickly delivered, meticulously dissected out, prepped, and viewed under a light microscope. The results demonstrated that 30 days of exposure to Naf in drinking water produced liver damage manifested by significant increases in blood ALT, AST, and GGT activity as well as significant elevation in serum bilirubin (direct, indirect and total) concentration compared to control group. A significant rise in blood glucose levels and a fall in blood insulin levels and IR were detected at the end of the experiments in Naf treated group when compared to the control. Histopathological changes in Naf treated group was observed in hepatic and pancreatic tissue manifested by generalised degeneration and necrosis of hepatocytes, in addition, to severe degeneration of acinar and pancreatic islet cells. In conclusion, the findings of this investigation revealed Naf therapy-induced liver damage and a change in the glycemic index in adult male rats.