Saffron has therapeutic applications in a range of neurodegenerative conditions, notably Parkinson's disease (PD). Crocin I, a principal bioactive constituent of saffron, demonstrates neuroprotective potential in PD models. However, its precise molecular mechanisms remain incompletely elucidated. Network pharmacology served as the methodology for investigating the mechanistic basis of crocin I in PD. Predictions from bioinformatics analysis were experimentally validated using a rotenone-induced PD mouse model. To verify the predicted targets and pathways, Western blotting, molecular docking, and RT-qPCR, were utilized. HPLC quantification confirmed that crocin I constitutes a major component of saffron, accounting for 13.9% (w/w) of the extract. Integration of network pharmacology, molecular docking, and molecular dynamics simulations indicated that crocin I exerts its effects through the modulation of key targets. This involves key targets including SRC, HRAS, and PTPN11, along with regulation of the PI3K-AKT signaling pathway. In vivo evidence supported these predictions, showing that crocin I attenuated motor dysfunction and protected to dopaminergic neurons. RT-qPCR and Western blotting analyses further confirmed that crocin I treatment downregulated the mRNA expression of SRC, HRAS, and PTPN11, upregulated PIK3R1 and AKT1 mRNA levels. The ratios of p-AKT/AKT and p-PI3K/PI3K proteins were increased. Collectively, these findings indicate that crocin I mitigates neuroinflammation and dopaminergic neuron loss through the regulation of SRC, PTPN11, and HRAS, along with the activation of the PI3K-AKT signaling pathway, thereby supporting its potential as a therapeutic agent for PD.