Abstract： Background: Comorbidity is common and causes poor stroke outcomes. We aimed to examine the modifying impacts of physical activity (PA) and diet quality on the association between comorbidity and disability in stroke patients. Methods: A cross-sectional study was conducted on 951 stable stroke patients in Vietnam from December 2019 to December 2020. The survey questionnaires were administered to assess patients’ characteristics, clinical parameters (e.g., Charlson comorbidity index items), health-related behaviors (e.g., PA using international physical activity questionnaire), health literacy, diet quality (using dietary approaches to stop hypertension quality (DASH-Q) questionnaire), and disability (using world health organization disability assessment schedule II (WHODAS II)). Linear regression models were used to analyze the associations and interactions. Results: The proportion of comorbidity was 49.9% (475/951). The scores of DASH-Q and WHODAS II were 29.2 ± 11.8, 32.3 ± 13.5, respectively. Patients with comorbidity had a higher scores of disability (regression coefficient, B, 8.24; 95% confidence interval, 95% CI, 6.66, 9.83; p < 0.001) as compared with those without comorbidity. Patients with comorbidity and higher tertiles of PA (B, -4.65 to -5.48; p < 0.05), and a higher DASH-Q score (B, -0.32; p < 0.001) had a lower disability score, as compared with those without comorbidity and the lowest tertile of PA, the lowest score of DASH-Q, respectively. Conclusions: Physical activity and diet quality significantly modified the negative impact of comorbidity on disability in stroke patients. Strategic approaches are required to promote physical activity and healthy diet which further improve stroke rehabilitation outcomes.