This disclosure provides compositions and related methods providing targeted cell-specific inhibition of Notch receptor signaling. The disclosure provides a bi-specific molecule with separate domains that target the intended cell-type and the Notch receptor on that cell-type. The disclosure also provides for nucleic acids, vectors, and cells allowing for the expression of the bi-specific fusion molecules. The disclosure also provides related methods of making and using the bi-specific fusion molecule to inhibit Notch signaling in target cells of interest, including for the treatment of diseases characterized by a dysregulation of Notch signaling.