Objective: Stress contributes to poor health outcomes; importantly, a stress reaction begins with the negative appraisal of a situation. The ability to use cognitive reappraisal, an emotion regulation strategy that involves reinterpreting an initial appraisal to change its emotional impact, could be a protective factor against the health consequences of stress reactivity. The present study investigated (a) if cognitive reappraisal ability (CRA) acts as a stress buffer against a body mass index (BMI) indicative of being overweight (≥25 kg/m2) or obese (≥30 kg/m2), and (b) if this buffering effect persists against the indirect influences of perceived stress reactivity (PSR) on Type 2 diabetes. Method: One hundred fifty participants (54% female; mean age = 40.4 years ± 12.4 years) completed an online CRA task, self-report measures of PSR, height, weight, and Type 2 diabetes diagnosis on Amazon’s Mechanical Turk. Results: Results revealed that CRA significantly interacted with PSR to predict BMI, which indirectly predicted Type 2 diabetes. Individuals with higher PSR and higher CRA exhibited BMIs within a normal weight range and lower incidence of Type 2 diabetes. In contrast, individuals with higher PSR and lower CRA were overweight or obese, with a higher incidence of Type 2 diabetes. Interestingly, higher CRA was not protective in those who had lower levels of PSR. Conclusions: Findings from this study suggest that emotion regulation interventions can be developed to indirectly target Type 2 diabetes and similar obesity-related illnesses, and that emotion regulation interventions should be tailored to the individual.