We conducted an oral mucosal irritation study in hamsters to evaluate a therapeutic apparatus using hydrogen peroxide (H2O2) photolysis for periodontitis treatment (ISO 10993-Part 10, Annex B.3). The cheek pouches in 15 male hamsters were allocated to one of six groups. Group 1 received pure water treatment (control group). Group 2 received laser irradiation at 80 mW. Group 3 received 3% H2O2. Groups 4–6 received laser irradiation of 3% H2O2 at 80, 40, and 20 mW, respectively. The total treatment time was set at 7 min and treatment was repeated three times at approximately 1-h intervals. Macroscopic and microscopic histologic observations of the treated sites were performed immediately after each treatment and/or 24 h after the last treatment. The mean scores in macroscopic and histologic examinations in all six groups were 0. Accordingly, irritation indices calculated by subtracting the mean score in each experimental group from that in the control group (Group 1) were 0. Our results suggest that treatment with the apparatus has no mucosal irritation potential in hamster cheek pouches under test conditions simulating clinical conditions.