In conventional dendrimer synthesis, producing defective dendrimers is unavoidable. However, no synthetic method exists to prepare these defect dendrimers with a well-defined structure. A novel and efficient solid-phase method has been developed to synthesize well-defined lysine defect dendrimers using orthogonally protected lysine residues. This chapter details the synthesis of two defect lysine dendrimers. Additionally, the synthesis of a boronic acid-decorated defect lysine dendrimer is presented to demonstrate the feasibility of this method for preparing functional defect dendrimers.