Rheumatoid　arthritis　(RA)　is　an　autoimmune　disease　characterized　by　destructive　effects.　Although　current　therapies　utilizing　antibodies　against　inflammatory　cytokines　have　shown　some　success,　the　inhibition　of　a　single　inflammatory　molecule　may　not　suffice　to　impede　the　progression　of　RA　due　to　the　intricate　pathogenesis　involving　multiple　molecules.　In　this　study,　we　have　developed　an　intelligent　transformable　peptide,　namely　BP-FFVLK-DSGLDSM　(BFD).　BFD　has　the　ability　to　self-assemble　into　spherical　nanoparticles　in　water　or　in　the　blood　circulation　to　facilitate　their　delivery　and　distribution.　When　endocytosed　into　immune　cells,　BFD　can　identify　and　attach　to　phosphorylation　sites　on　IκBα　and　in　situ　transform　into　a　nanofibrous　network　coating　NF-κB/IκBα　complexes,　blocking　the　phosphorylation　and　degradation　of　IκBα.　As　a　result,　BFD　enables　decreasing　expression　of　proinflammatory　mediators.　In　the　present　study,　we　demonstrate　that　BFD　exhibits　notable　efficacy　in　alleviating　arthritis-related　manifestations,　such　as　joints　and　tissues　swelling,　as　well　as　bone　and　cartilage　destruction　on　the　collagen-induced　arthritis　(CIA)　rat　model.　The　investigation　of　intracellular　biodistribution,　phosphorylation　of　IκBα,　and　cytokine　detection　in　culture　medium　supernatant,　joint　tissue,　and　serum　exhibits　strong　associations　with　therapeutic　outcomes.　The　utilization　of　transformable　peptide　presents　a　novel　approach　for　the　management　of　inflammatory　diseases.　©　2024　Elsevier　Ltd