Since its first introduction, levodopa has remained the cornerstone treatment for Parkinson’s disease. However, as the disease advances, the therapeutic window for levodopa narrows, leading to motor complications like fluctuations and dyskinesias. Clinicians face challenges in optimizing daily therapeutic regimens, particularly in advanced stages, due to the lack of quantitative biomarkers for continuous motor monitoring. Biochemical sensing of levodopa offers a promising approach for real-time therapeutic feedback, potentially sustaining an optimal motor state throughout the day. These sensors vary in invasiveness, encompassing techniques like microdialysis, electrochemical non-enzymatic sensing, and enzymatic approaches. Electrochemical sensing, including wearable solutions that utilize reverse iontophoresis and microneedles, is notable for its potential in non-invasive or minimally invasive monitoring. Point-of-care devices and standard electrochemical cells demonstrate superior performance compared to wearable solutions; however, this comes at the cost of wearability. As a result, they are better suited for clinical use. The integration of nanomaterials such as carbon nanotubes, metal–organic frameworks, and graphene has significantly enhanced sensor sensitivity, selectivity, and detection performance. This framework paves the way for accurate, continuous monitoring of levodopa and its metabolites in biofluids such as sweat and interstitial fluid, aiding real-time motor performance assessment in Parkinson’s disease. This review highlights recent advancements in biochemical sensing for levodopa and catecholamine monitoring, exploring emerging technologies and their potential role in developing closed-loop therapy for Parkinson’s disease.
