<p><i>Salmonella</i> spp. are the most important foodborne and zoonotic bacteria in the world, with severe implications for public health, food safety, and the economy. Antimicrobial peptides (AMPs) targeting the innate immune system and new therapeutic targets for conventional antibiotics are largely mediated through electrostatic adsorption onto microbial surfaces with membrane disruption or intracellular interference. However, <i>Salmonella</i> has also evolved complex mechanisms of resistance to reduce the effectiveness of AMPs, among which attachment to surfaces and lipopolysaccharide (LPS) modifications are among the main factors. This review addresses the molecular and structural basis of AMP recognition by the outer membrane of <i>Salmonella</i> focusing on binding involving anionic LPS and how peptide chemistry affects antimicrobial activity. The position of the LPS remodelling reactions is controlled by <i>PhoP</i>, <i>PhoQ</i>, <i>PmrA</i>, and <i>PmrB</i> two component sensor responders, which modify lipid A by adding amino arabinose and other substituents that reduce the negative charge, modify hydrophobicity, and lower AMP binding affinity. Other resistance mechanisms, including efflux systems, proteolytic degradation, and biofilm formation, have been studied in terms of binding evasion. In addition to mechanistic insights, this review also discusses the clinical and health implications of AMP resistance, considering zoonotic transmission, agricultural pressure, and cross-resistance to polymyxins. New therapeutic strategies include engineered AMPs with enhanced binding affinities, nano-delivery platforms, and synergistic combinations of AMPs with antibiotics. This review concludes by underlining the value of continued investigation of <i>Salmonella</i> surface binding and remodelling as critical drivers of AMP resistance and drug discovery.</p> Graphical Abstract <p></p>