Xanthine oxidase, a key enzyme of purine metabolism, is considered to be a prime target for the treatment of hyperuricemia and oxidative stress related disorders. Allopurinol and febuxostat are two FDA approved xanthine oxidase inhibitors currently being used for management of chronic hyperuricemia. Plethora of natural sources has been explored in search of novel chemical templates for the development of antihyperuricemic drugs. Studies in past decade have shown the potential of endophytic fungi, which colonize the internal tissues of plants without any evident sign of their ubiquitous existence, as repository of novel chemical entities exhibiting antimicrobial, anti-oxidant, anti-inflammatory and anticancer potential. However, very scanty preliminary data is available of exploration of xanthine oxidase inhibitors from fungal endophytes. The present review summarizes the efficacy of xanthine oxidase as target for developing ant-gout agents and highlights the prospective of endophytic fungi as producers of xanthine oxidase inhibitors for the anti-hyperuricemic therapy regimen.