Parkinson’s disease is a neurodegenerative disease that causes the death of dopamine-producing neurons. It is associated with the accumulation of a protein called α-synuclein, which is responsible for the death of the neurons and causes severe motor disorders. Current drugs have significant side effects and only treat symptoms rather than the actual disease. Our study aims to explore the anti-Parkinsonian effects of curcumin and nicotinamide, which are two compounds derived from natural sources. Curcumin and nicotinamide were chosen for their health benefits and properties that suggest anti-Parkinsonian potential. In our study, we used the model organism C. elegans, a nematode. Our strain expresses human α-synuclein fused to yellow fluorescent protein. The study examined the effect of curcumin and nicotinamide on the fluorescence intensity of α-synuclein in C. elegans and compared it to the effect of Levodopa (the commercial drug most commonly prescribed to Parkinson’s patients). We used two methods to measure fluorescence. In our first method, the worms were imaged after treatment under a fluorescence microscope, and fluorescence was quantified using ImageJ. In the second method, the fluorescence of the worms was measured after treatment using a microplate reader. Our study showed that curcumin and nicotinamide reduce the fluorescence intensity of α-synuclein as effectively as levodopa in C. elegans. This suggests that curcumin and nicotinamide may affect α-synuclein levels in other organisms and should be further investigated as treatments for Parkinson’s disease. These findings also encourage further investigations on other natural compounds as possible therapies against Parkinson’s disease.