Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting over five million patients worldwide. Like Alzheimer’s disease (AD), it mostly affects the elderly and causes considerable disability and suffering. Unfortunately, the molecular mechanism of PD is still poorly understood, and there are no drugs available to treat the disease. Our overall aim was to identify natural products to probe PD by phenotypic assay using human olfactory neurosphere-derived (hONS) cells from PD patients. The research presented in this thesis exemplifies the importance of natural products as chemical probes for further investigation of PD as well as lead compounds for future PD-drug development. The thesis begins with an introduction of PD and the chemotherapeutics for PD. It also covers a review on the natural origin anti-PD compounds and the analysis of their physicochemical properties using Lipinski’s rule of five. As part of a research program aiming to identify anti-PD chemical probes, a high throughput screening assay was developed to screen 4224 fractions. Twenty fractions were confirmed to display neuroprotective effects of the PD cells against rotenone. Seven prioritized fractions, representing one Australian marine sponge Jaspis splendens (subject 1) and two Australian terrestrial plants Gloriosa superba (subject 2) and Alangium villosum (subject 3), were selected for large scale extraction and isolation. The results were presented in Chapter 2 to 5.