An experiment was undertaken to evaluate the effects of garlic extract on hematological, biochemical, and histopathological profiles in F1 crossbred chicks (White Leghorn cops × Nigerian Heavy Ecotype chickens) non-infected and infected with Salmonella typhimurium. This experiment was carried out to contribute to the genetic improvement of local Nigerian chickens while controlling salmonellosis and combating antibiotic resistance. Two hundred and forty (240) chicks at two weeks old were randomly divided into six treatments: T1 (No Salmonella and no garlic), T2 (garlic only), T3 (Ciprofloxacin only), T4 (Salmonella + Ciprofloxacin), T5 (Salmonella + garlic) and T6 (Salmonella without garlic or ciprofloxacin) and reared for six days. On day seven, birds were sacrificed, and blood samples were collected for hematology and biochemistry analysis, while liver and small intestines were also collected for histopathology. Data obtained were subjected to analysis of variance (ANOVA), and were means were found to be significant, Duncan’s New Multiple Range Test was used to separate the means at a 5% probability level. The results revealed that white blood cell counts, neutrophils percentage, liver enzymes, total protein, and the weight of organs increased significantly on T6. In contrast, packed cell volume, red blood cell counts, and hemoglobin decreased significantly. Liver and small intestines damage were also observed. However, feeding birds with garlic counteracted the effect of ST on those parameters. It can be concluded that hexane extract of garlic can alleviate the harmful effect of ST in birds’ systems and, thus, used in Poultry Farms against antibiotic resistance.