Migraine is a common neurological disorder, and it is the second leading cause of disability worldwide. Manual techniques based on physical therapy have been proposed to improve migraine aspects; however, further research is needed on their effectiveness. The aim of this study was to evaluate the effectiveness of a craniosacral therapy protocol on different features in migraine patients. Methods: Fifty individuals with migraine were randomly divided into two groups (n = 25 per group): (i) craniosacral therapy group (CTG), following a craniosacral therapy protocol, and (ii) sham control group (SCG), with a sham treatment. The analyzed variables were pain, migraine severity and frequency of episodes, functional, emotional, and overall disability, medication intake, and self-reported perceived changes, at baseline, after a 4 week intervention, and at 8 week follow-up. Results: After the intervention, the CTG significantly reduced pain (p = 0.01), frequency of episodes (p = 0.001), functional (p = 0.001) and overall disability (p = 0.02), and medication intake (p = 0.01), as well as led to a significantly higher self-reported perception of change (p = 0.01), when compared to SCG. In addition, the results were maintained at follow-up evaluation in all variables. Conclusions: A protocol based on craniosacral therapy is effective in improving pain, frequency of episodes, functional and overall disability, and medication intake in migraineurs. This protocol may be considered as a therapeutic approach in migraine patients.