Gout, a metabolic disease, has increased steadily in prevalence worldwide, particularly among men and in regions with high socio-demographic index (SDI) values. The development of gout is strongly associated with hyperuricemia, a precursor condition. Currently, treatment options for gout and hyperuricemia are limited. The primary medications for both conditions fall into two categories: those that promote uric acid excretion and those that block uric acid formation. Both medication classes are frequently associated with a range of adverse effects. Therefore, it is particularly important to find new treatment methods. Xanthine oxidase (XO) is one of the key enzymes regulating uric acid production, and xanthine oxidase inhibitory peptides derived from marine shellfish show potential applications in this field. Small-molecule peptides may be more likely to have an inhibitory impact on XO. Peptides with xanthine oxidase inhibitors (XOI) action have been effectively isolated from a range of marine creatures. These peptides are predominantly neutral or slightly basic and commonly contain specific amino acid residues such as tryptophan (Trp). This chapter describes the preparation, isolation, purification, identification, and characterization of XO inhibitory peptides, and discusses their potential applications in treating gout and hyperuricemia. Though research into XO inhibitory peptides derived specifically from marine shellfish is still limited, existing studies offer both a theoretical basis and practical guidance for developing bioactive peptides from marine shellfish proteins.