<p>Pyrroloquinoline quinone (PQQ) is a naturally occurring redox-active compound with potent antioxidant, mitochondrial-enhancing, and neuroprotective properties. Originally identified as a cofactor in bacterial enzymes, PQQ has garnered significant interest for its potential therapeutic role in neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). It has reported that PQQ exerts its effects through several key molecular mechanisms, including the activation of antioxidant pathways via Nrf2/ARE signaling, enhancement of mitochondrial biogenesis and function through AMPK/PGC-1α, and the regulation of inflammatory processes through NF-κB inhibition. By improving cellular energy metabolism, reducing oxidative stress, and promoting neuronal survival, PQQ offers a multifaceted approach to counteracting the pathophysiological factors underlying neurodegeneration. Our review focusing on current study of PQQ on its enhancing neuroplasticity, and protecting neurons from damage induced by oxidative stress, mitochondrial dysfunction, and inflammation. Further we reviewed the significant signaling pathways that involved PQQ neuroprotective mechanisms, positioning it as a novel candidate for future therapeutic strategies targeting these debilitating conditions.</p>