Cholesterol is vital for the optimal growth and physiological function of Pacific white shrimp, Penaeus vannamei. Due to limited availability of fish meal, plant-based ingredients are increasingly added in the shrimp diet which limit the availability and utilization of cholesterol. This study investigated the synergistic effects of dietary taurine and cholesterol supplementation on growth and physio-metabolic responses of Pacific white shrimp, Penaeus vannamei fed with high plant-based protein diets reared in a biofloc system for 60 days. A basal diet (control) comprised 82.55 % plant-based ingredients and 36 % crude protein. Five isonitrogenous and isolipidic diets were prepared (T1-T5) with cholesterol and taurine supplements at inclusion levels of 0.15 % and 0.16 % in T1 and T2, respectively. In the rest of the treatments, T3, T4, and T5, the combinations of cholesterol and taurine were 0.15 % and 0.16 %; 0.05 % and 0.24 %; 0.25 % and 0.08 %, respectively. The experimental diets were allocated to triplicate groups of 100 shrimp per tank following a completely randomized design. The results showed that shrimp fed T3 diet have a significantly (P < 0.05) higher percentage of weight gain, specific growth rate (SGR), percentage of survival, and protein efficiency ratio (PER) with efficient feed conversion ratio (FCR) (1.14±0.06) compared to other treatments. The hematological, antioxidant, and digestive enzyme activities, except amylase activity, were significantly (P < 0.05) higher in shrimp fed T1 and T3. Total bile acid content in T3 fed shrimp was higher than in other dietary treatments (P < 0.05). The results indicated that supplementing a combination of 0.15 % cholesterol and 0.16 % taurine in a high plant-based diet significantly improved growth performance, nutrient utilization, and physio-metabolic responses of P. vannamei.