The therapeutic misuse and overuse of antibiotics leads to the rapid emergence of antibiotic-resistance bacteria. Antibiotic-resistant bacteria can induce cross-protection against environmental stresses, resulting in the acquisition and spread of multiple antibiotic resistance. Therefore, this study aimed to assess the resistance phenotype and genotype of cefotaxime- and ciprofloxacin-induced resistant Salmonella Typhimurium exposed to acid, heat, and NaCl. The antibiotic susceptibilities of wild-type (WT) S. Typhimurium ATCC 19585 and WT S. Typhimurium KCCM 40253 were decreased after cefotaxime (CET) and ciprofloxacin (CIP) induction. The highest β-lactamase activities were observed at the WT and CET-induced S. Typhimurium CCARM 8009, showing more than 3 nmol/min/ml. The dominant FT-IR spectra at the region from 1700–1500 cm-1 represent proteins such as amide II and III at the CET-induced S. Typhimurium ATCC19585 and CIP-induced S. Typhimurium KCCM 4025. The CET- and CIP-induced S. Typhimurium strains showed better survival at pH 4.5 and 4% NaCl than the WT strains. The highest expression levels of ompC and rpoS were observed at CIP-induced S. Typhimurium KCCM 40253 when exposed to sublethal stresses of pH 4.5, 4% NaCl, and heat at 48oC. This study provides useful information for assessing the cross-protective responses of antibiotic-resistant bacteria to environmental stresses.