Mesial temporal lobe epilepsy (MTLE) is a prevalent form of drug-resistant epilepsy characterized by focal seizures originating from the hippocampus and surrounding structures. Neurostimulation provides an alternative to surgery-ineligible patients with intractable seizures. Hippocampal low-frequency stimulation (LFS) has shown antiepileptic effects in animal studies and small clinical cohorts, yet its long-term effects and mechanisms remain unclear. This study investigates LFS effects on different types of epileptiform activity, spatial learning and anxiety, and synaptic plasticity.We used the intrahippocampal kainate mouse model that recapitulates the main pathological features of MTLE: recurrent spontaneous seizures, hippocampal sclerosis, and cognitive comorbidities. We implanted recording electrodes into each hippocampus and a stimulation electrode into the sclerotic hippocampus. Continuous stimulation at 1 Hz for 6 hours daily was repeated four times a week for one month alongside local field potential recordings. During the fourth and fifth stimulation week, we performed behavioral tests comprising open field, light-dark box, and Barnes maze. After LFS, mice were immediately sacrificed for histological analysis and electron microscopy. Hippocampal LFS consistently suppressed focal seizures without waning effects over time, but it did not affect generalized seizures with behavioral correlates. While epileptic mice displayed impaired spatial memory and anxiety-like behavior, long-term LFS did not alter these aspects. Examination of synapses near the stimulation site ruled out vesicle depletion as the antiepileptic mechanism. Furthermore, LFS did not alter hippocampal sclerosis, neurogenesis, or glutamatergic synapses. In summary, long-term hippocampal LFS effectively reduces focal seizures without impacting generalized seizures, behavior, or histopathological features associated with MTLE.