The Wnt signaling pathway has a significant regulatory part in tissue development and homeostasis. Dysregulation of the Wnt signaling pathway has been associated with many diseases including cancers and various brain diseases, making this signaling pathway a promising therapeutic target for these diseases. In this review, we describe the roles of the Wnt signaling pathway in the blood-brain barrier (BBB) in intracranial tumors and peripheral tumors, from preclinical and clinical perspectives, introduce Wnt-regulated therapeutics including various types of drugs and nanomedicines as BBB modulators for brain-oriented drug delivery and as therapeutic drugs for cancer treatments, and finally discuss limitations and future perspectives for Wnt-regulated therapeutics.