<p>Biofilms are surface-attached bacterial consortia, which account for 80% of the world’s microbial biomass, and are responsible for 75% of human infections. These surface bacterial communities have enhanced their ability to withstand unfavourable conditions and resist antimicrobial treatments due to the presence of outer membrane proteins (OMPs). Outer membrane proteins (OMPs) play a central role in biofilm formation by mediating adhesion, matrix assembly, and intercellular interactions, and they are increasingly being targeted for novel antibacterial therapies to disrupt biofilm-related infections. OMPs play a crucial role in biofilm formation, as these proteins contribute to the assembly and architecture of the biofilm matrix, interact with other matrix proteins, and influence surface hydrophobicity and cell aggregation. Notably, genetic modifications or deletions of OMPs can increase or decrease biofilm formation, indicating their regulatory influence on matrix composition and biofilm morphology. Incidentally, biofilm poses significant challenges in industry and abiotic medical equipment. OMPs offer excellent targets to mitigate biofilm-forming infections, since blocking their function can reduce bacterial adhesion and disrupt biofilm integrity. Furthermore, antimicrobial peptides as well as nanotechnology-based therapeutics are under development to target OMPs, allowing for innovative approaches that circumvent traditional resistance mechanisms seen in biofilms. This review underscores the significance of key OMPs in devising strategies to combat biofilm-associated infections and offers a concise overview of their structure, function, and immunoprotective role. By targeting outer membrane proteins, emerging therapies seek to address the persistence and antibiotic resistance of biofilm-forming bacteria, representing a promising direction in the treatment of chronic and multidrug-resistant infections.</p>