Abstract: Successful feed acclimation of mandarin fish (Siniperca chuatsi) to formulated feed has made precise prevention and control of viral diseases through medicated diets possible. To evaluate the anti-largemouth bass ranavirus (LMBV) activity of Abrus cantoniensis extracts and their application potential in the domesticated culture of pellet-fed mandarin fish, we systematically compared the in vitro anti-LMBV effects of the aqueous extract (ABE) and ethanol extract (ABAE), and further assessed their prophylactic efficacy and protective effects against LMBV via feeding administration combined with pathogen challenge assays. The results showed that the maximum safe working concentrations of ABE and ABAE in mandarin fish brain-derived CPB cells were 62.5 and 1.95 μg·mL⁻¹, respectively. Both ABE and ABAE inhibited LMBV replication, whereas ABE exhibted a stronger inhibitory effect. ABE exerted inhibitory activity during the adsorption, entry, and replication stages of viral infection, with the strongest effect observed at the replication stage. In the challenge test following 14 d of continuous dietary administration, the survival rate of fish in the 1600 mg·kg⁻¹ ABE group increased to 66.67%, with a relative percent survival (RPS) of 56.52%. In addition, viral loads in the liver, spleen, and kidney were continuously reduced, and the abnormal expression of IL-8, TNF-α, and HSP70 genes in the spleen and kidney was alleviated. Histopathological analysis showed that ABE relievedLMBV-caused splenic rarefaction and structural disintegration, as well as degeneration of renal tubular epithelial cells. In the feed-training trial with juvenile mandarin fish, dietary supplementation with 800 mg·kg⁻¹ ABE increased antioxidant enzymes indices, including T-SOD, GSH-Px, and GR, in serum and liver, while decreasing the levels of MDA, TG, T-CHO, ALT/GPT, and AST/GOT, thereby improving the basal health status of juvenile fish. The results indicate that dietary supplementation with 1 600 mg·kg⁻¹ ABE exerts a protective effect in mandarin fish after LMBV infection, whereas supplementation with 800 mg·kg⁻¹ ABE during the feed-training period improves the health status of juvenile fish. Therefore, the aqueous extract of A. cantoniensis has potential for development as a functional feed additive or therapeutic agent for the prevention and control of LMBV infection.