The efficacy of diet and its influence on gut microbiome composition has been largely demonstrated in inflammatory bowel disease (IBD). Little is known about its potential in the management of extraintestinal manifestations. We report a successful application of Crohn disease exclusion diet (CDED) in association with infliximab and methotrexate, as salvage therapy in a child affected by chronic recurrent multifocal osteomyelitis (CRMO) and Crohn disease (CD) resistant to optimized therapy. Both intestinal and bone symptoms remitted after the application of CDED. Diet may have acted on common microbic inciting agents that trigger both intestinal and bone inflammation, supporting the role of microbiota in the pathogenesis of IBD-associated extraintestinal manifestations. Our experience suggests the potential benefit of CDED in association with combined therapy in resistant patients affected by CD and extraintestinal manifestations.