Siganus fuscescens, an economically important species in southern China, is noted for its rapid growth and high nutritional value. Nonetheless, the prevalence of darkening syndrome, a condition marked by skin discoloration and significant mortality rates, presents a challenge to aquaculture practices, with its etiology remaining largely unexplored. This study aimed to examine the impacts of varying dietary lipid levels and multivitamin supplementation on the incidence of darkening syndrome in S. fuscescens. Five experimental diets were developed: a low-fat diet containing 10% lipids; a moderate-fat diet with 13% lipids; a moderate-fat diet with 13% lipids supplemented with multivitamins; a high-fat diet containing 16% lipids; and a high-fat diet with 16% lipids supplemented with multivitamins. A 55-day feeding trial was conducted on S. fuscescens specimens. The results indicate that, in this experiment, increasing dietary fat content led to a higher cumulative incidence of darkening syndrome in S. fuscescens. Serological and histological findings suggested that in the 16% lipid diet group, S. fuscescens exhibited liver injury and oxidative stress. Notably, supplementation with multivitamins alleviated these adverse effects. Overall, we recommend using an appropriate dietary fat level and further supplementing with antioxidant multivitamins, which may represent an effective strategy to mitigate darkening syndrome in S. fuscescens.