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To overcome the intrinsic resistance mechanisms of bacteria, End\u2010alkyl\u2010modified dipiperazine\u2010phenyl derivatives are designed via convergent molecular platforms (CMPs)\u2010guided multi\u2010target directed ligand (MTDL) strategy. These dual\u2010functional compounds not only inhibit the AcrB\u2010TolC efflux pump system but also enhance bacterial membrane permeability and display a distinctive activity profile across a broad concentration range. Through integrated evaluation combining in vitro activity screening and computational ADMET (absorption, distribution, metabolism, excretion, toxicity) profiling, compound C5 is identified as a promising lead candidate. This compound achieved three notable breakthroughs. First,\u00a0it reduces biofilm formation by 80% at 1\/64 minimum inhibitory concentration (MIC) when combined with antibiotics. 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