In this study, the anti-inflammatory effect of dental pulp mesenchymal stem cell (MSCs) exosomes loaded to mucoadhesive hydrogel is investigated in a dental nickel hypersensitivity murine model. After culture of dental pulp MSCs in the third passage MSCs are loaded to a mucoadhesive hydrogel based on chitosan, cross-linked with genipin and modified with catechol groups. A dental nickel hypersensitivity model is created by administering NiCl and 10 µg mL lipopolysaccharide to 4-6 week-old Balb-c mice by intradermal injection. In mice treated with dental pulp MSC exosomes and exosomes in hydrogel, interferron gamma (IFN-γ) secreting CD4+T lymphocyte ratios significantly increase compared to the untreated group (p < 0.05). IFN-γ and interleukin 10 (IL-10) expression in buccal mucosa tissue sections and IFN-γ secreting CD4+T lymphocyte ratios are found to be significantly higher in mice treated with dental pulpa MSCs (DPMSCs) exosomes and DPMSCs exosomes in hydrogel compared to the untreated group (p < 0.05). According to flow cytometry results, IL-4 secreting CD4+T lymphocytes are found to be significantly decreased in DPMSCs exosomes group compared to dental nickel hypersensitivity group (p < 0.05). Administration of DPMSCs exosomes with mucoadhesive hydrogel may be an alternative to current medication in the treatment of dental nickel hypersensitivity.