Purpose <p>Gastrointestinal cancers represent a significant global health burden, particularly in East Asia where incidence and mortality rates remain high. Although chemotherapy is a primary treatment strategy, its adverse effects often undermine treatment adherence and patient well-being. This study aimed to examine the psychosocial determinants of self-management behaviors in gastrointestinal cancer patients undergoing chemotherapy by applying a structural equation modeling (SEM) approach.</p> Methods <p>A cross-sectional study was conducted among 753 gastrointestinal cancer patients receiving chemotherapy at eight tertiary hospitals in China. Participants completed validated instruments assessing self-management behaviors, self-efficacy, medical coping strategies, perceived social support, and psychological distress. Structural equation modeling was used to investigate the direct, indirect, and mediating effects among the variables.</p> Results <p>The SEM analysis revealed that self-efficacy had both a direct and indirect positive effect on self-management behaviors, mediated by adaptive coping strategies. Perceived social support was significantly associated with increased self-efficacy and adaptive coping, while psychological distress negatively influenced self-management, primarily through reduced self-efficacy and increased maladaptive coping. The final model demonstrated good fit indices (CFI = 0.950, TLI = 0.933, RMSEA = 0.065), supporting the hypothesized relationships.</p> Conclusions <p>Self-management in gastrointestinal cancer patients undergoing chemotherapy is influenced by a complex interplay of psychosocial factors. Interventions that target self-efficacy enhancement, encourage adaptive coping, and strengthen social support systems may be critical to improving treatment adherence and patient outcomes.</p>