Pancreatic cancer remains one of the most lethal malignancies, characterized by limited therapeutic options and poor prognoses. Here, we report the development of novel dual-targeting PROTAC (proteolysis-targeting chimera) compounds designed to concurrently degrade GSK-3β and CDK5. These bifunctional molecules were systematically designed by integrating three critical components: (1) a ligand that selectively binds GSK-3β and CDK5, (2) an E3 ligase-recruiting motif, and (3) an optimized linker to facilitate target engagement and proteasomal degradation. Our series of compounds (DBMG-01 through DBVR-PTC-02) demonstrated robust and selective target degradation in pancreatic cancer cell lines, achieving nanomolar DC