<p>Neurosteroids (NSs) are endogenous progesterone derivatives that act as natural allosteric modulators of GABA_A ​receptors, exerting distinct effects from conventional receptor agonists. They play critical roles in modulating neuronal excitability, cognitive function, and stress responses, and have shown potential in mitigating seizure severity and frequency, particularly in temporal lobe epilepsy (TLE). TLE is a common drug-resistant focal epilepsy characterized by complex pathophysiology involving hippocampal sclerosis, neuroinflammation, synaptic dysfunction, and alterations in GABA_A ​receptor subunits. Accumulating evidence indicates that NSs, including Allopregnanolone, brexanolone, and ganaxolone, may exert neuroprotective and anti-epileptogenic effects through both direct GABAergic modulation and indirect regulation of mTORC1, AMPK, and BDNF signaling pathways, as well as autophagy activation. Experimental studies demonstrate that NSs can prolong the latent period before epilepsy onset, reduce seizure recurrence, and potentially improve cognitive outcomes. However, clinical findings remain inconsistent, and prolonged NS exposure may lead to reduced receptor sensitivity. This review synthesizes current knowledge on the mechanistic roles of NSs in TLE, highlighting their potential as adjuvant therapies alongside antiepileptic drugs. Further translational studies are warranted to clarify optimal dosing strategies, identify patient subgroups most likely to benefit, and develop targeted NS analogues for refractory TLE management.</p>