Purpose <p>The standard lifelong treatment for Hashimoto’s thyroiditis (HT), a chronic autoimmune disease, is levothyroxine (LT4) therapy. Despite LT4 replacement therapy, patients continue to experience persistent fatigue, deterioration in psychological and general well-being. Our study was conducted to investigate the effects of photobiomodulation therapy (PMBT) combined with LT4 replacement therapy on fatigue and behavioural status in patients with HT.</p> Methods <p>Sixty patients with HT were randomised to receive active or sham PMBT twice weekly for three weeks. Clinical evaluations of the participants were performed before and at the third months after treatment. Fatigue was assessed using the Fatigue Impact and Severity Scale, sleep quality and sleepiness using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, and behavioural status using the Beck Anxiety and Depression Inventory.</p> Results <p>At the end of the treatment fatigue severity, sleep quality, daytime sleepiness and behavioural status were improved in both groups. In the between-group comparisons, all clinical symptom states showed a significant improvement in favour of the active group (<i>p</i> &lt; 0.05).</p> Conclusions <p>As a result, we concluded that PMBT is an effective method to reduce clinical symptoms in patients with HT.</p>