Salmonellosis is an infectious disease triggered by bacteria of the genus Salmonella. Its transmission occurs after the consumption of contaminated food and/or beverages. Currently, 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 pharmacologically known molecule for its activity in the central nervous system and its role as a psychostimulant. However, its immunomodulatory activity against bacterial infections has been explored, and thus, this study aims to evaluate the activity of a compound formed by caffeine associated with the antibiotic gentamicin against experimental models of Salmonella Typhimurium infection. Initially, the cytotoxicity of the compound was evaluated in cultures of peritoneal macrophages (pMØ), followed by pMØ cultures exposed to an inoculum of S. Typhimurium infected for 4 hours and subsequently treated with the compound for 24 hours to assess viability and quantify 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 compared to the DMSO 50% control group, but there was no reduction in the number of intracellular CFU. In the in vivo model, the compound also did not promote a reduction of CFU in the spleen, liver, and mesenteric lymph nodes. After the analysis of leukocyte quantification and cytokine gene expression, it will be possible to observe whether there was anti-inflammatory activity, and tissue samples will also be analyzed to measure whether the compound was able to attenuate histological damage.