Cancer-related fatigue (CRF) is a complex and common issue for many cancer survivors. CRF is a complex multidimensional symptom with poorly understood etiology, wide variation in severity between individuals, and a negative impact on multiple aspects of a cancer survivor’s life. The limited evidence-based options to manage CRF highlight a critical need to determine the acceptability, safety, and efficacy of novel interventions for CRF. This dissertation is grounded in the Theory of Unpleasant Symptoms. The purpose of this manuscript dissertation is to assess the acceptability, effectiveness, and safety of natural products for the treatment of CRF through two integrative reviews, a retrospective descriptive study, and a prospective descriptive cross-sectional study.