Inflammatory bowel disease (IBD) can manifest both macroscopically and microscopically in the oral cavity; however, little is known about salivary changes in IBD. Therefore, this study aimed to assess salivary and circulatory inflammatory profiles in IBD and to compare their potential to reflect the presence and activity of IBD. We measured 92 known inflammatory proteins in serum and in unstimulated and stimulated whole saliva samples from patients with IBD with active intestinal inflammation (n = 21) and matched control patients (n = 22) by proximity extension assay. Fifteen of the patients with IBD returned 10 to 12 weeks after treatment escalation for resampling. Sixty-seven of the proteins were detected in all 3 sample fluids but formed distinct clusters in serum and saliva. Twenty-one inflammatory proteins were significantly increased and 4 were significantly decreased in the serum of patients with IBD compared with that of the control patients. Two of the increased serum proteins, IL-6 and MMP-10, were also significantly increased in stimulated saliva of patients with IBD and correlated positively to their expressions in serum. None of the investigated proteins in serum or saliva were significantly altered by IBD treatment at follow-up. Overall, inflammatory proteins in serum correlated to biochemical status, and salivary proteins correlated positively to clinical parameters reflecting disease activity. Saliva and serum inflammatory profiles in IBD share a similar composition but reflect different aspects of disease activity. The oral cavity reflects IBD through elevated IL-6 and MMP-10 in stimulated saliva.