Alkaloids are widespread in plants, particularly in the Fabaceae family, and several are used as aquafeed supplements to increase immunity and stress resistance in farmed animals. Alkaloids are Janus-faced not only in terms of the doses used, but also in terms of the compound itself: There are alkaloids that have predominantly adverse effects, even at low doses, and other alkaloids that have many beneficial effects on the consumer. Even berberine, which is often supplemented and appears to have only beneficial activity, can have harmful activity. This reinforces the argument that, for safety reasons, toxicity studies should always be conducted before adding any alkaloid to aquafeeds. This chapter summarizes the current state of knowledge on supplemental alkaloids in aquafeeds and identifies gaps, such as quantitative structure-effect relationships, bioinformatics, and artificial intelligence to end the almost purely empirical status of this research field