We studied the amelioration potential of jambul (Syzygium cumini) fruit extract (JE) on fluoride ion (F) mediated behavioral alterations and hepato-nephronal histopathologies in four groups (n=10 per group) of adult male mice. Two groups, control (C) and jambul (J), were fed F-free water for 15 days while the other two groups, NaF (F) and NaF + jambul (F+J), were given 50 ppm F (from NaF) in drinking water on days 1–10 and F-free water + 0.25mL JE 12-hourly on days 11–15. The daily water intake in each group was recorded for the first 10 days. All animals were subjected to performance behaviors (balance beam bar, orientation, and climbing activities) on days 11–15 (post F-exposure period) and sacrificed to recover liver and kidneys on day 16. The organs were processed for microtomy and H & E staining. The daily water intake throughout the F-exposure period (days 1–10) in C and J groups remained constant apart from minute fluctuations while a persistent gradual decline was observed in F and F+J group animals. The mean water consumption (mL/g body weight/day) was significantly lower in F (0.0878±0.00239) and F+J (0.0873±0.00238) than in C (0.1231±000.597) and J (0.1229±0.0006) groups. Although the mean time taken to complete the balance beam bar, orientation, and climbing activities decreased gradually during the period of study (days 11–15) in all 4 groups, it remained persistently higher in F and F+J groups than in C and J groups. Hepatic histopathologies observed in F group animals included cytoplasmic vacuolations and disfigured nuclei of the hepatocytes, misaligned hepatic cords, and enlarged sinusoids and central lobular veins. Reversal of these pathological signs, with hepatic tissue regeneration and rehabilitation of the hepato-lobular arrangement, was seen in F+J group. No obvious signs of pathology were seen in histological sections of kidney in F group. Micrometric data revealed significantly higher (p 0.05) mean percent fractional weight of liver and cross-sectional area (CSA) of hepatocytes in F (6.23±0.32 g/100 g bw and 317.26±12.08 u2, respectively) than C (5.3±0.25 g/100 g bw and 270.09±9.1 u2), J (5.15±0.19 g/100 g bw, and 247.37±7.24 u2) and F+J (5.72±0.15 g/100 g bw, and 179.21± 5.9 u2) groups. The nephronal micrometric data for the endothelial brush border thickness of the proximal tubules and the CSAs of glomeruli and proximal tubules showed significantly lower mean values in F (4.92±0.38 u, 1712.9±97.6 u2, and 816.8±34.88 u2, respectively) as compared to C (6.66±0.17 u, 2265.8±110 u2, and 1283±66.12 u2), J (6.92±0.13 u, 1898±113.2 u2, and 1097.3±35.3 u2) and F+J (6.91±0.16 u, 1841.6±95.3 u2, and 1042.4±43.3 u2) groups. Conversely the mean luminal CSA of the proximal tubules was significantly increased in F (199.6±14.06 u2) compared to C (123.1±5.56 u2), J (88.12±5.25 u2), and F+J (119.1±6.94 u2) groups. The results showed that fluoride exposure in mice leads to various hepato-renal histopathologies and alterations in performance behaviors. These toxicities were convincingly ameliorated with JE treatment.