Objectives: The primary objective of this study is to explore the relationship between personality traits and self-rated health (SRH) in individuals with diabetes, while also comparing these associations with a group of healthy controls. Methods: The data for this study were obtained from the UK Household Longitudinal Study (UKHLS), comprising a sample of 1860 diabetes patients and 12,915 healthy controls who were matched in terms of age and sex. Hierarchical linear regression was utilized to analyze the data. The analysis included demographic variables such as age, sex, monthly income, highest educational qualification, marital status, and psychological distress assessed through the GHQ-12, personality traits, including Neuroticism, Agreeableness, Openness, Conscientiousness, and Extraversion, and diabetes status (0 for diabetes patients, 1 for healthy controls) as predictors. Interactions between personality traits and diabetes status were also included as predictors, with SRH serving as the dependent variable. Additionally, separate multiple regression analyses were conducted for diabetes patients and healthy controls, incorporating demographic variables, psychological distress, and personality traits as predictors, while SRH remained the dependent variable. Results: The findings of this study indicate that diabetes significantly moderates the association between Neuroticism and SRH. Specifically, both Neuroticism and Extraversion were negatively associated with SRH, whereas Openness and Conscientiousness exhibited a positive association with SRH in healthy controls. However, among diabetes patients, only Conscientiousness showed a positive association with SRH. Conclusion: Personality traits predict SRH in people with and without diabetes differently. Healthcare professionals and clinicians should try to come up with ways that improve SRH and thus better outcomes in diabetes patients based on the findings from the current study.