Abstract: Objective To investigate the effects of physical activity and disease burden on self-efficacy and quality of life in patients with inflammatory bowel disease (IBD). Methods A total of 312 IBD patients were selected by convenience sampling method. General information of patients was collected. Self-efficacy Chronic Disease Management Self-Efficacy Scale (CDM-SES), physical activity International Physical Activity Questionnaire-Short Form (IPAQ-SF), disease burden Inflammatory Bowel Diseases Disk (IBD-disk) Scale and quality of life Inflammatory Bowel Disease Questionnaire (IBDQ) were assessed in IBD patients. The chain-mediating effects of physical activity and disease burden on self-efficacy and quality of life in IBD patients were analyzed. Results There were statistically significant differences in self-efficacy of IBD patients with different ages, body mass index(BMI), places of residence, marital status, educational background and disease stages (P<0.05); there were statistically significant differences in physical activity among IBD patients with different gender, age, place of residence, marital status, education background, disease stage and whether to use biological agents (P<0.05); there were statistically significant differences in the disease burden of IBD patients with different BMI, place of residence, marital status, education background, payment method and disease stage (P<0.05); there were statistically significant differences in the quality of life of IBD patients with different ages, places of residence, marital status, education levels, payment methods, disease stages and whether to use biological agents (P<0.05). The quality of life of IBD patients was positively correlated with self-efficacy and physical activity (r=0.605, 0.482, P<0.01), and negatively correlated with disease burden and disease stage (r=-0.550, -0.362, P<0.01). Physical activity and disease burden partially mediated between self-efficacy and quality of life in IBD patients. Conclusion IBD patients exhibited moderate levels of self-efficacy, low levels of physical activity, and high disease burdens. Clinical healthcare professionals should actively take measures to improve patients' self-efficacy and physical activity levels to reduce disease burden.