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The unique enzymatic mechanism of Nsp15 has attracted considerable attention as a potential therapeutic target, and the identification of its inhibitors could facilitate the development of novel antiviral agents against coronaviruses. Although biochemical and structural studies have provided important insights into Nsp15 function, no comprehensive review has yet focused on computational approaches applied to the discovery of Nsp15 inhibitors. Consequently, this study aims to address this gap by summarizing recent in silico research focused on the structure, function, and inhibition of Nsp15. Special attention is given to inhibitors derived from both natural and synthetic sources, as well as their binding interactions and predicted pharmacological potential. 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