Background and Objectives: Myasthenia gravis (MG), a rare chronic neuromuscular disorder, is characterized by progressive physical decline and requires long-term pharmacological treatment. Due to the decline of physical and social abilities, MG patients are in great need of social support, including tangible and emotional support. This study aims to examine the association between social support and medication compliance and the possible mediating effects of mental distress and self-efficacy among MG patients. Methods: A cross-sectional analysis of a nationwide MG registry was conducted on 865 patients under oral medication treatment in China between June and July 2022. Validated scales were used to measure the respondent’s mental distress (Four-item Patient Health Questionnaire), social support (Modified Medical Outcomes Study Social Support Scale), self-efficacy for medication use (Self-efficacy for Appropriate Medication Use Scale), and medication compliance (Morisky Medication Adherence Scale, MMAS). The association between social support and medication compliance and possible mediating effects of mental health and self-efficacy were tested by structural equation model (SEM), with significant demographic and disease-related factors adjusted. Results: The respondents showed a very low level of medication compliance (71.2% poor compliance; 1.4% high compliance; mean MMAS=4.65). SEM showed that the association between social support and medication compliance was fully mediated by two indirect paths, including through self-efficacy (p<0.05, proportion mediated=63.8%) and through mental distress and then self-efficacy (p<0.05, proportion mediated=6.7%). Self-efficacy may be an essential variable in explaining the relationship between social support and medication compliance. Patients with higher levels of social support may demonstrate better mental health and higher self-efficacy for medication use, which may be a driver of higher medication compliance. Conclusions: It is imperative to improve medication compliance among MG patients. In addition to meeting the need of social support, assessment of and interventions on self-efficacy for medication use and mental health may facilitate improvement in medication compliance.