Abstract <p>Temporal Lobe Epilepsy with Hippocampal Sclerosis (TLE-HS) presents a significant therapeutic challenge, primarily due to pharmacoresistance and progressive hippocampal neurodegeneration. Since current anti-seizure therapies often provide limited seizure control in TLE-HS, there is increasing interest in exploring alternative and complementary treatment approaches. Chinese herbal medicine (CHM) or Traditional Chinese medicine (TCM) has gained attention for its multifaceted therapeutic potential, particularly its neuroprotective and anticonvulsant effects. This review explores preclinical and emerging clinical evidence supporting the efficacy of TCM in modulating key molecular targets involved in epileptogenesis. Several TCM-derived bioactive compounds exhibit anti-inflammatory properties by downregulating proinflammatory cytokines and damage-associated molecular patterns. Additionally, TCMs promote neurotrophic factor expression and enhance synaptic plasticity, thereby supporting neuronal survival. By balancing excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission, TCM may reduce seizure susceptibility and progression. Notably, herbs such as <i>Gastrodia elata</i> and <i>Uncaria rhynchophylla</i> demonstrate promising mechanistic effects. Although encouraging, these findings necessitate further pharmacological validation and clinical trials to substantiate TCM as a complementary, evidence-based intervention for patients with pharmacoresistant TLE-HS.</p>