We have identified a homeostatic response in a Scn1a+/- mouse model of Dravet syndrome (DS), a developmental and epileptic encephalopathy caused by genetic variants of the SCN1A gene, leading to loss of function of the NaV1.1 sodium channel and consequent hypoexcitability of GABAergic neurons. Strikingly, we observed that cholecystokinin (CCK)-positive basket cells are hyperexcitable, unlike other GABAergic neurons, leading to increased release of CCK, which is a neuromodulator that can increase the excitability of other GABAergic interneurons. We have boosted this homeostatic response in a therapeutic approach. In fact, we performed chronic intranasal administrations of a modified degradation-resistant CCK peptide and evaluated the effect on both seizures and behavioral abnormalities. First, we have tested the effect of CCK on hyperthermic seizure induction and we found an increase of seizure threshold, positively correlated with the dose. In a separate series of experiments, we evaluated the effect of chronic CCK treatment on spontaneous seizures. We observed a significant reduction in spontaneous seizure frequency in the CCK-treated mice, compared to the vehicle-treated controls. Subsequently, we performed a battery of behavioral tests on a different cohort of juvenile mice that underwent chronic CCK treatment. We have found no significant effect on hyperactivity or anxiety, but a rescue of sociability and memory dysfunctions. Importantly, we have not observed any adverse effects of CCK. Overall, CCK may be a therapeutic approach in DS.