AIM: The aim of this study was to assess the ameliorative effects of naringin (NR) on cognitive impairment in schizophrenia(SZ) from multiple perspectives using behavioral, histopathological and molecular biological approaches. MATERIALS AND METHODS: SZ models were established in rats RESULTS: NR was found to mitigate cognitive decline in learning and memory induced by MK-801. It lowered serum levels of IL-6 and HCY, reduced neuronal damage in the CA1 region of the hippocampus, increased the thickness of postsynaptic dense material, decreased the distance between synaptic gaps, decreased the expression of SIK1, and elevated the expression of miR-25-3p, CRTC2 and CREB1 in the hippocampus. CONCLUSION: NR may protect neurons in the CA1 region of the hippocampus and enhance synaptic plasticity by regulating the miR-25-3p/SIK1/CRTC2/CREB1 signaling pathway, thereby promoting cognitive improvement.