Multi‐omics and biochemical techniques further reveal that chiral NPs interfere with the chemokine axis (CX3CL1/CX3CR1)‐NF‐κB‐NLRP3 and PI3K‐AKT signaling pathways, regulate communications between neurons, neural stem cells and microglia (“the three‐body problem”), and induce anti‐inflammatory efficacy of microglia mitochondrial energy metabolic reprogramming in PD. Here, CX3CL1 is linked to Parkinson disease.