Parkinson's disease (PD), the second neurodegenerative disease characterized by the loss of dopaminergic neurons and formation of the Lewy body, is a leading cause of morbidities among the aging population. Surgery, deep brain stimulation and chemotherapy are some of the existing clinical treatment options. Unfortunately, none of them can stop the progression of PD. Considering the convenience of therapy, improved chemotherapy is more promising. Various studies have discovered excessive reactive oxygen species (ROS) in the midbrains of PD patients, which trigger mitochondrial dysfunction and facilitate the formation of α-synuclein (α-syn) neurotoxic oligomers, ultimately leading to the loss of dopaminergic neurons. Therefore, clearing excessive ROS is a desirable strategy for PD therapy. Matrine (MA), a naturally occurring alkaloid that can upregulate Nrf2 and relieve oxidative stress caused by excessive ROS, has great potential for treating PD. However, the blood-brain barrier (BBB), which prevents all large molecules and 98% of small molecules from entering the parenchyma, limits its applications. The photothermal effect offers an advanced strategy for crossing the BBB transiently and reversibly increasing its permeability. Black phosphorus nanosheets (BPNSs) are neoteric two-dimensional nanomaterials with excellent biocompatibility and drug loading capability. They are also commonly used as a promising photothermal agent that can open the BBB when exposed to 808 nm near-infrared radiation. Furthermore, BPNSs have a high antioxidant ability, which is thought to reduce excessive ROS in the PD brain. Herein, we utilized BPNSs as an MA carrier, developed a BPNSs-MA delivery system, and used the photothermal effect of BPNSs to increase BBB permeability and boost MA accumulation in the brain, resulting in synergistic BPNSs and MA PD therapy. This study was supported by the Guangdong Basic and Applied Basic Research Foundation (2019B1515120043), the Research Fund of University of Macau (File no. MYRG2019-00121-ICMS and MYRG2018-00207-ICMS) and the Science and Technology Development Fund, Macau SAR (File no. 0098/2020/A).