Abstract: Mulberry leaf extract possesses various functions, including growth promotion, antioxidative properties, immune enhancement, and antiviral effects, thereby potentially reducing the use for drugs in the breeding process. This study investigates the impact of mulberry leaf extract on the nonspecific immunity and antioxidant capacity of spotted sea bass. Three hundred and sixty striped spotted sea bass, initially weighing (9.00±0.02) g and in good physical health, were randomly divided into 6 groups. Each group was replicated 3 times, with 20 fish per replication. Over a 52d period, the fish were fed with feed containing different concentrations of mulberry leaf extract (0, 3, 6, 9, 12 and 15 g/kg). Results indicated that compared to the control group, mulberry leaf extract significantly increased IgM content in serum, peaking at an addition of 6 g/kg (P<0.05). However, mulberry leaf extract showed no significant effect on serum ACP, AKP, LZM, complement C3, and TP (P>0.05). Similarly, adding mulberry leaf extract to the feed had no significant effect on ACP and AKP activities in the head kidney of spotted sea bass (P>0.05). Furthermore, mulberry leaf extract significantly elevated serum CAT, SOD activity, and GSH levels, while notably reducing serum MDA content (P<0.05). T-AOC in spotted sea bass serum was unaffected by mulberry leaf extract (P>0.05). Additionally, mulberry leaf extract did not significantly alter SOD activity, T-AOC, and MDA content in the head kidney of spotted sea bass (P>0.05). The transcriptional analysis indicated that mulberry leaf extract could regulate the immune function of the spotted sea bass head kidney by directly or indirectly influencing tryptophan metabolism. However, mulberry leaf extract had no significant effect on the expression of certain genes in the head kidneys of spotted sea bass, such as 3-hydroxyanthranilic acid 3, 4-dioxygenase, beta-1, 4-N-acetylhexosaminyltransferase 3, phosphatidylcholine phospholipase C, MHC I antigen, and immunoglobulin heavy chain. These findings suggest that mulberry leaf extract can enhance the antioxidant capacity and nonspecific immunity of spotted sea bass serum and head kidney to a certain extent, providing a theoretical basis for its application in aquaculture.