The role of the nervous system in lifespan regulation remains poorly understood. Previous studied showed that several drugs blocking serotonin receptors could extend Caenorhabditis elegans (C. elegans) lifespan. However, little is known concerning whether drugs targeting other neurological system could extend C. elegans lifespan. Here, we report that aripiprazole, a widely used atypical antipsychotic drug, could robustly extend the lifespan (> 50%) and healthspan (> 80%) of C. elegans. Strikingly, as a dopamine D2-like receptor (D2R) agonist, aripiprazole extends lifespan through the signaling of dopamine, a neurotransmitter which is previously unknown to regulate lifespan. Among two D2R expressed in worms, aripiprazole-mediated lifespan extension is dependent on DOP-2, but not DOP-3. In addition, aripiprazole extends lifespan through a dietary restriction (DR) mechanism mediated by the AMPK/FOXO pathway. We also identified the DAG-PKC/PKD pathway as the bridge between dopamine receptors and the conventional DR pathway to transmit longevity signals. Our results present a novel finding that aripiprazole holds potential as a novel safe anti-aging drug, and identified a novel DR mechanism regulated by dopamine signaling which could be a promising direction for developing anti-aging interventions.