Preliminary evidence suggests that low-intensity pulsed ultrasound (LIPUS) has neuroprotective effects on ischemic stroke, depression, and other conditions leading to neuronal cell death (e.g., Parkinson's disease). The purpose of this study was to investigate the neuroprotective effects of LIPUS in epileptic mice. Mice were made epileptic through kainic acid (KA) administration and then stimulated with LIPUS. The neuroprotective effect of ultrasound was evaluated by observing the latency, anxiety-like behavior, and levels of proteins related to inflammation, apoptosis, or signaling pathways. The safety of LIPUS was assessed by hematoxylin and eosin (H&E) and Nissl stainings. LIPUS prolonged the latency (Sham: 6.00 ± 0.26 days; 1-kHz pulse repetition frequency (PRF): 7.00 ± 0.31 days), improved the anxiety-like behavior, and inhibited the expression of inflammatory factors and apoptosis-related proteins. In addition, H&E and Nissl staining results confirmed that LIPUS did not damage the brain. These findings suggest that LIPUS has neuroprotective effects in mice with KA-induced epilepsy. LIPUS may offer a new therapeutic approach to epilepsy.