The advances in bioinformatics and biomedicine have promoted the development of biomedical imaging and theranostic systems to respectively extend the endogenous biomarker imaging with high contrast and enhance the therapeutic effect with high efficiency. The emergence of biomacromolecule‐functionalized aggregation‐induced emitters (AIEgens), utilizing AIEgens, and biomacromolecules (nucleic acids, peptides, glycans, and lipids), displays specific targeting ability to cancer cell, improved biocompatibility, reduced toxicity, enhanced therapeutic effect, and so forth. This review summarizes the rational design of biomacromolecule‐functionalized AIEgens and their biomedical applications in recent ten years, including high‐resolution optical imaging of cell, tissue, and small animal model with low background; the biomarker detection for early diagnosis and prognosis; the delivery and monitoring of prodrugs; image‐guide photodynamic therapy and its combination with chemotherapy. Through illustrating their functional mechanisms and application, it is hoped that this review would open up a completely new train of research thought for attracted researchers in various fields.