Background. Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. People with T2DM are at risk of experiencing periodontitis and likely require treatment. Using data from the national multicenter Diabetes and Periodontal Therapy Trial (DPTT), the authors assessed patient-based characteristics associated with the clinical response to nonsurgical therapy. Methods. The DPTT investigators randomly assigned adults with T2DM (hemoglobin A1c [HbA1c] ≥ 7 percent and < 9 percent) and moderate to advanced periodontitis to receive immediate or delayed therapy (scaling and root planing, oral hygiene instruction, chlorhexidine rinse). The investigators assessed probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and medical conditions at baseline, three months and six months. Six-month changes in mean PD, CAL and BOP defined the treatment response. Complete data were available for 473 of 514 DPTT participants. The authors used multiple regression models to evaluate participant-level factors associated with the response. Results. More severe baseline PD, CAL and BOP were associated with greater improvements in these same measurements (P < .0001). Hispanic participants experienced greater improvements in PD and CAL than did non-Hispanic participants (P < .0001). Obese participants (those with a body mass index > 30 kilograms per square meter) experienced greater reductions in PD and BOP than did participants who were not obese (P < .001). Age, sex, HbA1c values, diabetes duration, and smoking were not associated with change in any outcome (P > .1). Conclusions. In patients with T2DM, baseline disease severity was associated with the clinical response to nonsurgical periodontal therapy. Body mass index and Hispanic ethnicity—but not glycemic control, diabetes duration or smoking—also may be useful in predicting clinical changes in this population. Practical Implications. These findings could help clinicians identify patients with T2DM who may or may not respond well to initial periodontal treatment.