Abstract Aquaculture is an important source of high‐quality protein and plays a crucial role in ensuring global food security. However, viral diseases have caused significant damage to aquaculture production, making it necessary to develop effective measures to treat them. Although drugs are commonly used to treat viral diseases, recent studies have shown that crude extracts of medicinal plants and their active ingredients have potential applications in the treatment of aquatic viral diseases. Furthermore, natural small molecule compounds from herbs could be used as lead compounds to develop more potent anti‐aquatic virus derivatives. As such, there is an urgent need to develop and apply drugs for the treatment of viral disease outbreaks in aquaculture. In this review, we summarize previous studies on the efficacy of different agents used as antiviral drugs in aquaculture, with a focus on their protective effects. Additionally, we highlight the potential of active natural compounds isolated from medicinal plants, which could serve as lead compounds for developing aquatic‐specific drugs. However, the relationship between the structure of a compound and its antiviral activity in aquaculture has not been clearly elucidated, posing a challenge for further drug optimisation. Therefore, this study also analyses the structure–activity relationship of several reported lead compounds and their derivatives in aquaculture, providing a reference for subsequent drug development efforts.