This systematic review assessed studies that evaluated the immunological traits of patients with both inflammatory bowel disease (IBD) and periodontal disease. An electronic search for literature was conducted on PubMed, Embase, Scopus, Cochrane and Web of Science. Studies that evaluated the immunological response in patients with IBD and periodontal disease were considered eligible for inclusion. A total of 6 cross-sectional studies of 275 patients were included. Immunological analyses were performed in gingival crevicular fluid, saliva, serum, intestinal and gingival biopsies. Four studies identified that the presence of IBD and periodontal disease was associated with higher levels of prostaglandin E2, aMMP8, IL-18 and S100A12, respectively, when compared to patients without the coexistence of both diseases. Furthermore, another study identified higher aMMP-8 levels with increasing severity of periodontitis in Crohn’s disease patients. The quality of overall evidence ranged from high to low due to the observational nature of contributing studies. The coexistence of IBD and periodontal disease seems to be associated with a more responsive inflammatory reaction compared with individuals having one or the other. More randomized controlled studies evaluating the coexistence of IBD and periodontitis are required to better explore the immunological interplay between them.