Seizure clusters, a severe form of epilepsy requiring urgent intervention, are challenging to manage in out-of-hospital settings due to limitations of traditional benzodiazepine administration routes. Diazepam nasal spray (DZP-NS), a novel intranasal formulation, achieves rapid absorption through the nasal mucosa, bypassing first-pass metabolism, with bioavailability comparable to rectal gel and faster onset. Clinical studies demonstrate its high efficacy in treating seizure clusters and prolonged seizures (≥5 minutes), with an initial control rate of 87.4% and low second-dose utilization (12.6%). No severe adverse reactions, such as cardiorespiratory depression, were observed. Long-term use (12 months) showed no tolerance development, significantly extending seizure intervals (SEIVAL) (from 12.2 to 25.7 days) and improving quality of life scores, particularly in "epilepsy-related concerns" and "social functioning" domains. The non-invasive delivery method was favored by over 80% of patients and healthcare providers for its convenience compared to rectal administration. Subgroup analyses confirmed consistent safety and efficacy across genders, ages, concomitant medications (including cannabidiol), and patients with allergy histories. In conclusion, DZP-NS provides an efficient, safe, and socially accepted out-of-hospital rescue therapy for seizure clusters, positioning it as a potential cornerstone in standardized epilepsy emergency care.