Parkinson’s disease (PD) is a common, progressive, and currently incurable neurodegenerative movement disorder. The diagnosis of PD is challenging, especially in the differential diagnosis of parkinsonism and in early PD detection. Due to the advantages of machine learning such as learning complex data patterns and making inferences for individuals, machine-learning techniques have been increasingly applied to the diagnosis of PD, and have shown some promising results. Machine-learning-based imaging applications have made it possible to help differentiate parkinsonism and detect PD at early stages automatically in a number of neuroimaging studies. Comparative studies have shown that machine-learning-based SPECT image analysis applications in PD have outperformed conventional semi-quantitative analysis in detecting PD-associated dopaminergic degeneration, performed comparably well as experts’ visual inspection, and helped improve PD diagnostic accuracy of radiologists. Using combined multi-modal (imaging and clinical) data in these applications may further enhance PD diagnosis and early detection. To integrate machine-learning-based diagnostic applications into clinical systems, further validation and optimization of these applications are needed to make them accurate and reliable. It is anticipated that machine-learning techniques will further help improve differential diagnosis of parkinsonism and early detection of PD, which may reduce the error rate of PD diagnosis and help detect PD at pre-motor stage to make it possible for early treatments (e.g., neuroprotective treatment) to slow down PD progression, prevent severe motor symptoms from emerging, and relieve patients from suffering. CLICK TO REVIEW