Background <p>The management of insomnia in patients with myasthenia gravis (MG) poses a clinical challenge, as MG is a well-recognized contraindication to sedative-hypnotic agents. This retrospective study aimed to assess the efficacy and safety of low-dose trazodone hydrochloride for the management of insomnia in MG patients.</p> Methods <p>Clinical data were collected from MG patients with comorbid insomnia who received low-dose trazodone hydrochloride (25–100&#xa0;mg, once nightly, for ≥ 4 weeks). Enrolled patients were stratified into three groups based on Self-Rating Depression Scale (SDS) scores: pure insomnia group (SDS: 0–52), mild depression group (SDS: 53–62), and moderate-to-severe depression group (SDS ≥ 63). Changes in Pittsburgh Sleep Quality Index (PSQI) scores, SDS scores, and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before and after trazodone hydrochloride administration were analyzed.</p> Results <p>Total 68 MG patients were enrolled, including 17 cases of ocular MG and 51 cases of mild generalized MG. Of these patients, 18 (26.5%) were assigned to the pure insomnia group, 30 (44.1%) to the mild depression group, and 20 (29.4%) to the moderate-to-severe depression group. Post-treatment PSQI scores were significantly reduced compared to baseline across all groups (all <i>p</i> &lt; 0.01). The mild depression group exhibited a significant decrease in SDS scores after treatment (<i>p</i> &lt; 0.01), whereas no significant reduction in SDS scores was observed in the moderate-to-severe depression group. No patients experienced an increase in MG-ADL scores. Mild adverse events were reported in 4 patients (5.9%), including hypotension (<i>n</i> = 2), dizziness (<i>n</i> = 1), and nausea (<i>n</i> = 1).</p> Conclusions <p>Low-dose trazodone hydrochloride demonstrates favorable efficacy and safety in improving insomnia in patients with stable and mild MG.</p>