Peptides have numerous biological applications, such as the development of PROTAC. In 2018[1], we designed a stabilized peptide-based proteolysis-targeting chimera (PROTAC) targeting estrogen receptor α (ERα) by tethering an N-terminal aspartic acid cross-linked stabilized peptide ERα modulator (TD-PERM) with a pentapeptide that binds the Von Hippel–Lindau (VHL) E3 ubiquitin ligase complex. In 2022[2], we reported a proximity-triggered group transfer strategy from a sulfonium warhead to a Cysteine (Cys) residue of the target protein. With a guiding ligand, cargoes could be transferred selectively from a sulfonium center in sulfonium 1-X onto the Cys residue in the vicinity of their binding interface. In 2023[3], we reported a UBE2C-targeting bioPROTAC based on the NEL (novel E3 ligase) domain of bacterial E3 ligase IpaH9.8 and the UBE2C-binding WHB (winged-helix B) domain of APC2 (anaphase promoting complex subunit 2). In the same year [4], we proposed a split-and-mix nanoplatform that serves as a self-adjustable platform capable of facile screening, programmable ligand ratios, self-optimized biomolecule spatial recognition and multifunctional applications. We highlight the scope of our platform through the targeted disruption of intracellular therapeutic targets, involving ERα, CDK4/6, AR, MEK1/2, BRD2/4, BCR-ABL, etc. These studies confirm the effectiveness and universality of the SM-PROTAC platform for proximity-induced applications. This platform is programmable, with significant potential applications to biomolecule regulation, including the fields of epigenetics, gene editing, and biomolecule modification regulation.