Collectively, the current study shows a neuroprotective potential of calycosin on PQ-induced PD-like phenotypes using Drosophila as a model organism, as evidenced by improved DA neuronal health, locomotor performance, and increased fly survival, primarily governed by lower ROS (O2•−/ONOO−) formation, pJNK-caspase-3 mediated neuronal cell death, and improving mitochondrial functions and restoring autophagy in exposed organism (Figure 8). Here, CASP3 is linked to Parkinson disease.