Background: Multiple Sclerosis is an inflammatory-demyelinating disease of the central nervous system that may produce severe levels of disability in the long term. This disease affecting more than 2 million people worldwide and it is the second leading cause of disability in young adults after trauma. Self-management is crucial to managing individuals with multiple sclerosis as advance their prognosis by learning about many aspects of the illness as well as closely monitoring their own health with their care providers. The study was aimed to evaluate the effect of self-management guidelines on knowledge, fatigue, self-efficacy, and medications adherence among patients with multiple sclerosis. Study design: A quasi-experimental design was applied in the current study.