Indole and spiro-fused oxoindole frameworks widely exist in a variety of natural bioactive products, pharmaceuticals and drug candidates, featuring unique functions in the regulation of proliferation, infiltration, and metastasis of cancer cells. In recent years, significant progress of proteolysis targeting chimeric (PROTAC) technology that employs ubiquitin-proteasome system (UPS) to eliminate disease-associated proteins has been witnessed, thus opening a promising avenue to the discovery of new indole-related drugs. In this review, we focus on summarizing the achievements on small molecule PROTACs that involve indole/spiro-fused oxoindole scaffolds in the part of ligands of the protein of interest (POI). Current challenges and future directions in this promising field are discussed at the end of this review. For the convenience of readers, our review is divided into five parts according to the types of target proteins. We hope this review could bring a quick look and some inspiration to researchers in relevant fields.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.