People with physical disabilities report a higher prevalence of psychological distress and chronic stress than those without disabilities. Participation in physical activity (PA) has been considered an effective coping strategy to deal with stressors and improve the mental health of people with disabilities. However, very little research has been conducted to explore the relationship between disability-related stress and PA participation by people with physical disabilities longitudinally on an international scale. Therefore, the purpose of this study was to investigate the effect of different levels of PA participation on disability-related stress among people with physical disabilities longitudinally. This study used data from the second wave of the Korean Panel Survey of Employment for the Disabled (PSED) from 2016 to 2022. The results of generalised estimated equation modelling indicated that higher levels of PA participation were associated with lower disability-related stress levels over time in the Koreans with physical disabilities who participated in our study. Our findings suggest that participating in 130-150 min of PA per week is the optimal range for reducing disability-related stress. The practical implications of improving the mental health of people with physical disabilities and future research directions were discussed.