Salmonellosis is an infectious disease caused by bacteria of the genus Salmonella. Its transmission occurs after the consumption of contaminated food and/or beverages. In the current scenario, antibiotic therapy has been used to control the infection; however, the increase in resistance to antimicrobial agents reveals the need to search for new therapeutic protocols. Caffeine is a molecule pharmacologically known for its activity in the central nervous system and as a psychic stimulant. However, its immunomodulatory activity against bacterial infections has been explored. Therefore, this study aims to evaluate the activity of a compound formed by caffeine associated with the antibiotic gentamicin against experimental models of infection by Salmonella Typhimurium. Initially, the cytotoxicity of the compound was evaluated in peritoneal macrophage cultures (pMØ). Then, pMØ cultures were exposed to an inoculum of infected S. Typhimurium for 4h and subsequently treated with the compound for 24h to evaluate the viability and quantification of Colony Forming Units (CFU). In an in vivo model of salmonellosis, mice were infected orally and received daily treatment for 5 days post-infection (dpi). The results indicated that the compound is not cytotoxic and, after infection and treatment, pMØ treated with 5 μg/mL CAF + 10 μg/mL GEN showed greater viability when compared to the 50% DMSO control group, but there was no reduction in the number of intracellular CFU. In the in vivo model, the compound did not promote the reduction of CFU in the spleen, but mice treated with 5 μg/mL CAF + 10 μg/mL GEN did not show bacterial growth in the liver. Total and differential quantification indicated a reduction in the number of leukocytes in the blood of the mice. Together, the results indicate that the compounds were not efficient in combating the infection.