Parkinson's disease (PD) is a common chronic central nervous system disorder that reduces quality of life and increases mortality. Currently, the treatment of PD is limited due to the challenge of macromolecular drugs crossing the blood‐brain barrier (BBB). Black phosphorus (BP) has antioxidant and anti‐inflammatory effects and shows potential for neuroprotection. To solve the restriction of the BBB, we constructed innovative BP microbubbles (BP@MBs) combined with focused ultrasound (FUS) to facilitate BBB opening. Additionally, we investigated the biocompatibility and safety of BP@MBs with varying dimensions, including BP quantum dot microbubbles (BPQDs@MBs) and BP nanosheet microbubbles (BPNSs@MBs). Our findings indicate that low concentrations of BP had good biosafety and that BPQDs@MBs exhibit better biocompatibility than BPNSs@MBs both in vitro and in vivo at the same concentrations. Moreover, we established a 6‐OHDA‐induced PD cell model and an animal model to verify the anti‐PD effects of BPQDs@MBs and BPNSs@MBs. The results confirmed that BPQDs@MBs and BPNSs@MBs had antioxidant effects that reduced neuronal apoptosis and improved the motor symptoms of PD in rats. Furthermore, BPQDs@MBs exerted anti‐inflammatory effects to regulate an intestinal flora imbalance induced by 6‐OHDA, which had excellent anti‐PD efficacy. BPQDs@MBs combined with FUS may be a promising option for the clinical treatment of PD.This article is protected by copyright. All rights reserved