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The present study aimed to evaluate antidiarrheal potential of prickly pear cladode and its hepatoprotective role in different groups of diarrhea‐induced mice. Mice received cefixime (4 mg/kg of bw) and different concentrations of aqueous cladode extract (250 mg/kg of bw, 500 mg/kg of bw and 1000 mg/kg of bw). Feces Salmonella typhi ATCC 19430 was used to assess antidiarrheal potential and hematological, biochemical parameters, and histopathological analyses were carried out for 17 days. The results showed that administration of Salmonella typhi ATCC 19430 in mice produced liver injuries with histological damage, whereas 1000 mg/kg of bw cladode extract reduced the Salmonella typhi ATCC 19430 load of feces earlier as compared to the other groups during 17 days. Hematological parameters, like red blood cells (RBCs) (6.19 ± 1.85 × 106/mm3) and hemoglobin (Hb) (10.06 ± 2.03 g/dL), of negative control group decreased, while white blood cells (WBCs) (13.46 × 106/mm3) increased from reference values. In lipid profile, low‐density lipoprotein (LDL) (9.0 ± 2.41 mg/dL), high‐density lipoprotein (HDL) (6.07 ± 2.45 mg/dL) and total cholesterol (TC) (35.22 ± 8.29 mg/dL) of negative control group decreased, while triglycerides (TG) (168.35 ± 71.75 mg/dL) increased from reference values. Alanine transferase (ALT) (60.30 ± 20.33 IU/L), alkaline phosphatase (ALP) (359.9 ± 100.05 IU/L) and aspartate transferase (AST) (168.77 ± 66.61 IU/L) of negative control group increased from reference values. Urea (27.36 ± 10.54 mmol/L) and creatinine (35.29 ± 12.15 mmol/L) of the negative control group increased. Cefixime also ameliorated injuries due to the administration of Salmonella typhi ATCC 19430. Conclusively, these findings indicated that pure aqueous extract of cladode showed more promising results regarding antidiarrheal potential. Hence, cladode might be used in food and supplement formulations as a functional ingredient. [ABSTRACT FROM AUTHOR]