Abstract Although nucleotides ( NT ) have long been implicated as feed attractants in both vertebrate and invertebrate species, research into potential growth and health benefits of dietary NT in aquaculture species has just been implemented in early 2000s. To date, research pertaining to NT supplementation in aquafeed as functional nutrients has shown rather consistent and encouraging, beneficial results in fish and shrimp health management. Dietary NT serve a marked role to enhance growth in early stages of development, improve reproductive performances of brood fish, enhance larval quality, increase stress and disease resistance, modulate immune functions and improve intestinal morphology and gut microbiota of fish and shrimp. NT have also been used as functional supplement in alternative protein based diet, where NT was found as an effective supplement to increase the efficiency of utilizing alternative proteins. However, still there are numerous gaps in existing knowledge about exogenous NT administration to fish and shrimp including various aspects of digestion, absorption, metabolism, administration duration and age/size‐related responses. Adoption of different molecular technologies, like proteome modification and study of several gene expression pattern related to growth, immunity, gut health and stress resistance in details are important for exploring the underlying mechanisms of NT functions in improved growth and health performances of fish and shrimp. Efforts are also needed on production technologies to reduce the NT cost. Moreover, extensive research information is also required regarding the use of NT in alternative protein and lipid based diet to develop cost‐effective, ecofriendly functional aquafeed in near future.