Proteus mirabilis, a key catheter-associated urinary tract infection pathogen that forms antibiotic-resistant crystalline biofilms, was shown via multi-omics analyses to be multimodally inhibited by succinic acid. At 15 mM, succinic acid reduced the bacterium’s growth by 70% and biofilm formation by 50%. Metabolomics revealed dysregulation in tryptophan/arginine metabolism, nucleotide biosynthesis, and the tricarboxylic acid cycle; transcriptomics showed downregulated ribosomal genes, oxidative phosphorylation, and efflux pumps plus upregulated arginine transport; and proteomics demonstrated suppressed T6SS virulence factors and iron acquisition proteins. Mechanistically, succinic acid is proposed to reduce K6 acetylation of the histone-like nucleoid structuring protein, enhancing its oligomerization to repress T6SS genes and inhibit biofilm formation. By targeting metabolism, virulence, and stress adaptation, succinic acid circumvents single-target resistance, offering a strategy to combat multidrug-resistant P. mirabilis via biofilm disruption and pathogenicity suppression.The uploaded data comprise two omics datasets:Acetyl-proteomics: Folders prefixed with XB10893DPAc (treatment: H1–H3; control: T1–T3)；Proteomics: Folders prefixed with XB10893DA (treatment: H1–H3; control: T1–T3).