Blood–brain barrier dysfunction plays a key role in the development and progression of neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, and brain injuries from trauma. The structural and functional integrity of the blood-brain barrier is essential for maintaining balance in the central nervous system. It allows selective permeability and protects neurons from changes in the environment. The link between blood–brain barrier dysfunction and a failed autophagy process involves several mechanisms, including lysosomal trapping, mammalian target of rapamycin 1 (mTORC1) overactivation, and endoplasmic reticulum stress. New treatment approaches can aim to restore blood–brain barrier function and support autophagy with pharmacological inhibitors, antioxidants, gene-editing techniques, senolytics, and interventions that regulate the microbiota. Challenges with drug delivery pose significant issues for targeting the blood–brain barrier. Improvements in organoids from patients, computational screenings for new drugs, and microfluidic models of the blood–brain barrier offer promising new options for better neuroprotection.