The applications of nanotechnology in medical sciences, especially in drug and gene delivery, has experienced unprecedented growth in recent years. The integration of nanomaterials into pharmaceutical formulation and delivery strategies has sparked significant innovations in therapeutic agent delivery systems. In recent years, there has been considerable interest in polymer brush-based drug and gene delivery systems due to their immense application potential. The aim of designing and developing such delivery systems is to create a platform with efficient drug/gene loading, controlled release, extended half-lifetime, and low toxicity. Molecular polymer brushes, a category of high-density side-chain-grafted copolymers, offer diverse nanostructures formed by attaching polymeric side chains to a linear backbone. These polymer brushes exhibit distinct structures and properties, making them innovative tools for crafting “smart” materials tailored for targeted therapeutic agent delivery because of their responsiveness to various stimuli such as ultrasound, electrical/magnetic field, mechanical stresses, light, temperature, and pH changes. Over recent years, researchers have synthesized diverse polymer brush architectures with the aim of developing nanomaterials for various biomedical applications including cancer diagnosis, treatment, biosensors, and contributions to cell biology and regenerative medicine. This article provides a comprehensive overview of latest advancements in designing and preparing molecular polymer brushes, highlighting their potential as promising candidate in the realm on biomedicine.