Neurodegenerative diseases (NDs) are a group of disorders characterized by the progressive loss of neuronal structure and function, leading to clinical manifestations such as cognitive decline, motor dysfunction, and neuropsychiatric abnormalities. NDs encompass a range of conditions, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), etc. With the intensifying trends of global population growth and aging, the incidence of NDs continues to rise, yet no curative treatments are currently available. The blood-brain barrier (BBB) plays a crucial role in maintaining central nervous system (CNS) homeostasis by blocking harmful substances in the bloodstream from entering brain tissue. More than 98% of small-molecule drugs and nearly 100% of large-molecule therapeutics fail to cross the BBB and reach brain parenchyma. Ultrasound-targeted microbubble destruction (UTMD) is an emerging interdisciplinary technology integrating materials science and bioengineering, which combines the advantages of microbubble carriers with the physical properties of ultrasound. This innovative approach enables transient and reversible opening of the BBB, and enhancing drug delivery efficiency. Microbubbles (MB) are the core component of the UTMD system, consisting of two fundamental structural elements: a gaseous core and a biocompatible outer shell. The drug-loading capacity of MB has been significantly expanded, evolving from traditional chemotherapeutic agents to encompass nucleic acid drugs, macromolecular antibodies, and even traditional Chinese medicines. Concurrently, their drug-loading strategies have advanced from initial passive physical adsorption to active targeted delivery. UTMD possesses the following 4 biological advantages. (1) UTMD can transiently and reversibly enhance the permeability of cell membranes and blood vessels. The biocompatible shells commonly used in microbubbles can be metabolized by the body, posing no risk of long-term accumulation. (2) UTMD not only significantly improves drug delivery efficiency but also simultaneously serves as an ultrasound contrast agent and therapeutic carrier, achieving the integration of diagnosis and treatment. (3) UTMD technology offers dual advantages of spatial targeting and molecular targeting, allowing for precise drug delivery. (4) UTMD only requires conventional ultrasound equipment, and the raw materials for microbubble preparation are readily available with simple synthesis processes. Whether applied in diagnostics or treatment, the cost remains relatively low. The mechanism by which UTMD opens the BBB is primarily associated with cavitation effect and sonoporation effect. The cavitation effect induces mechanical stretching of both cellular membranes and capillary walls, creating transient, reversible channels that facilitate macromolecular drug passage, to enhance BBB permeability. Meanwhile, the sonoporation effect promotes drug penetration through dual mechanisms: (1) augmenting passive diffusion across biological barriers; (2) potentiating active transport processes. This synergistic action significantly elevates both local drug concentrations and therapeutic efficacy at target sites. The permeability of BBB is predominantly influenced by both microbubble characteristics and ultrasound parameters. Microbubble characteristics and ultrasound parameters are key factors affecting BBB permeability. By adjusting the composition of microbubbles and optimizing ultrasound parameters, effective BBB opening can be achieved while minimizing tissue damage, to regulate the dosage of drugs delivered to the brain parenchyma. Both preclinical investigations and clinical trials have consistently shown that UTMD holds significant therapeutic promise for NDs. This article outlines the fundamental properties of microbubbles and elucidates the potential mechanisms underlying UTMD mediated BBB opening. Furthermore, it systematically reviews recent advances in UTMD technology for the treatment of treating various NDs, aiming to provide a theoretical foundation and future directions for developing novel therapeutic strategies and drugs for NDs.