Optimism is thought to be beneficial for health, and these effects may be mediated through modifications in psychophysiological stress reactivity. Type 2 diabetes (T2D) is associated with reduced cardiovascular responses to stress and heightened cortisol over the day. This study assessed the relationships between optimism, stress responsivity, and daily cortisol output in people with T2D. A total of 140 participants with T2D were exposed to laboratory stress. Heart rate (HR), systolic (SBP), diastolic blood pressure (DBP), and cortisol were measured throughout the session. Cortisol output over the day was also assessed. Optimism and self‐reported health were measured using the revised Life Orientation Test and the Short Form Health Survey. Optimism was associated with heightened SBP and DBP stress reactivity (ps < .047) and lower daily cortisol output (p = .04). Optimism was not related to HR, cortisol stress responses, or the cortisol awakening response (ps > .180). Low optimism was related to poorer self‐reported physical and mental health (ps < .01). Optimism could have a protective role in modulating stress‐related autonomic and neuroendocrine dysregulation in people with T2D.