Purpose <p>Numerous innovative treatment approaches have been developed to treat migraine, one of the most upsetting disorders. However, the optimal strategy for managing migraines remains unclear. The calcium channel blockers have demonstrated some positive effects on migraine attacks. In this systematic review, we tried to gather data on the efficacy and safety of these drugs to reach a more precise conclusion.</p> Method <p>The databases of PubMed, Scopus and Web of Science were searched systematically up to 1 August 2024. The risk of bias was assessed for clinical trials through the Cochrane Collaboration’s tool.</p> Results <p>Out of 1903 studies, we included 40 clinical trials. Among 27 studies on flunarizine (FLU), most of them showed significantly superior effects in comparison with placebo or other agents. Sedation and weight gain were the most prevalent side effects experienced by FLU. Although three studies demonstrated positive effects of nimodipine (NIM) in migraine management, the seven remaining studies revealed controversial results. Three and one articles evaluating the efficacy and safety of nifedipine (NIF) and verapamil (VER) to other drugs, respectively, reported no special effects.</p> Conclusion <p>According to reviewed research, FLU appears to have the greatest impact on migraine episodes, whereas NIM outperforms B blockers in terms of migraine prevention. Further study is necessary to get more precise data on NIF and VER.</p>