Background <p> Stroke and multiple sclerosis are two common neurological diseases, and fatigue symptoms are particularly prominent in patients with these diseases. Existing studies have shown that cognitive behavioral therapy has the potential to improve fatigue symptoms in patients with stroke and multiple sclerosis; however, the conclusions are inconsistent. This study aimed to evaluate the effects of cognitive behavioral therapy on fatigue in patients with stroke and multiple sclerosis.</p> Methods <p>PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM databases were searched from inception to November 2024. Two researchers screened the relevant literature on cognitive behavioral therapy for improving fatigue in patients with stroke and multiple sclerosis and extracted the data based on the inclusion and exclusion criteria. The quality of the literature was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0, and a meta-analysis was performed using RevMan 5.3.</p> Results <p>Twelve studies involving 723 patients were included in the analysis. Among them, one article had a quality evaluation of A, and seven articles had a quality evaluation of B. The results showed that compared with conventional interventions, cognitive behavioral therapy can improve fatigue, sleep, and depression-related symptoms in stroke patients, as well as fatigue and sleep symptoms in patients with multiple sclerosis. However, it was ineffective in alleviating anxiety symptoms in patients with stroke and multiple sclerosis.</p> &#xa0;Discussion <p> Cognitive behavioral therapy is an effective method for alleviating fatigue in patients with stroke and multiple sclerosis. However, further verification is needed through multicenter, large-sample randomized controlled trials.</p> Registration <p>PROSPERO (CRD42025637844).</p>