We used the acute NMDA receptor hypoactivity model of schizophrenia in mice to compare the efficacy of a long-term ketogenic diet and a commonly used antipsychotic, olanzapine, and to explore the interaction between these treatments. We found that a ketogenic diet in female mice was as effective as olanzapine to diminish MK-801-induced disruption of prepulse inhibition (PPI). Furthermore, combination of the diet with olanzapine treatment resulted in a similar effect compared to either treatment alone. These results suggest that ketogenic diet can be used effectively together with antipsychotics drugs over an extended period.