Transcranial Electric Stimulation (TES) has emerged as a promising non- or minimally-invasive therapeutic approach for drug resistant epilepsy treatment. However, the optimaltiming of stimulation relative to the ongoing brain oscillations remains to be established foroptimizing efficiency.This study investigates the phase specificity of transcranial ISP stimulation in terminatingepileptic seizures, using both animal models and clinical data. By analyzing deep-brainactivity during seizures in rats and post-hoc analysis of clinical data from human patientsunderwent closed-loop ictal stimulation, we unveil the optimal timing for intervention.In this study, we recorded intracranial EEG (iEEG) signals in electrically kindled rats, anddelivered phase targeted ictal transcranial stimulation by Intersectional Short-Pulsestimulation (ISP), allowing to map and understand the underlying neuronal activities at theseizure onset zone and their responses to the ISP stimulation.Our findings consistently demonstrate that closed-loop stimulation is effective in shorteningboth the seizure lengths and the proportion of the generalized segments, emphasizing thepotential clinical impact of phase-dependent intervention. Additionally, stimulating at, ornear the peak of seizure oscillations yield the most significant reductions in seizure duration.This phase-specific effect is further validated through data from our first-in-patient clinicalstudy performed to demonstrate the feasibility of closed-loop seizure termination in humanpatients.In conclusion, these insights not only refine therapeutic strategies, but also underscore thetranslational potential of preclinical models, in guiding personalized epilepsy care.Ultimately, understanding the phase dependence of closed-loop neurostimulationrepresents a critical step towards advancing epilepsy treatment.