Epilepsy is a primary study focus for scientists worldwide due to its prevalence and poor prognosis. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, is becoming increasingly recognized for its critical role in the pathophysiology and progression of epilepsy. The treatment of epilepsy remains challenging despite the discovery of numerous factors that contribute to the development of several beneficial medications. In recent years, many microRNAs have been linked to the progression of epilepsy because they target SIRT1 mRNA. SIRT1, which protects from epilepsy, has been reported to be upregulated by several natural compounds and their derivatives. This review will summarize the latest findings about SIRT1's role in epilepsy. Results from the literature indicate that SIRT1 is a promising target for epilepsy therapy.