As proven by the excessive osteoclastic activation, greater expression of RANKL and CTSK, the increases in 8-OHdG, γ-H2AX, COX-2, and IL-1β levels, and the decreases in RUNX2 and osterix levels in the periodontium of STZ-injected mice, all of our findings strongly suggest that diabetes-triggered periodontal destruction is the outcome orchestrated by imbalanced bone metabolism, oxidative stress, and inflammatory responses. The gene discussed is CTSK; the disease is diabetes mellitus.