The inclusion of exogenous digestive enzymes and probiotics is well established in the aquafeed industry. The mixture of multienzymes and probiotics improves the feed utilization and wellbeing of aquatic animals than the individual supplementation. Herein, we evaluated the exogenous multi-enzyme mixture (beta-glucanase, cellulase, alfa-amylase, protease, xylanase, and phytase) at 250 mg/kg and multi-species probiotic (Bacillus subtilis, Lactobacillus acidophilus, L. delbrueckii, L. rhamnosus, L. plantarum, and Pediococcus acidilactici; 1 × 1010 CFU/g for each bacterial strain) at 2 g/kg on the performances of Siberian sturgeon. The final weight, weight gain, SGR, and PER were markedly enhanced while the FCR was reduced in fish fed multienzyme and probiotics premix (P<0.05). Multi enzymes and probiotic mixture significantly increased the total body protein content (P˃0.05). Multi enzymes and probiotic mixture also improved the digestibility of crude protein, dry matter, and crude lipids nutrients (P<0.05). The count of Goblet cells, microvilli diameter, microvilli length, outer muscle wall diameter, and enterocyte total absorptive surface were markedly increased (P<0.05) by dietary multienzymes and probiotics mixture. The WBCs and neutrophils showed marked improvements (P<0.05). The levels of glucose, triglycerides, blood urea nitrogen, and total bilirubin were markedly higher in fish fed the control than fish fed the multienzymes and probiotics mixture (P<0.05). Significantly, Siberian sturgeon-fed dietary multienzymes and probiotics had improved lysozyme activity, total immunoglobulin, and total protein in the skin mucus and serum samples (P<0.05). Further, the serum complement C3 and C4 was higher in fish-delivered multienzymes and probiotic mixture than in control (P<0.05). In conclusion, dietary probiotics synergistically enhanced the activity of multienzymes and resulted in increased feed utilization, nutrient digestibility, and health status of Siberian sturgeon.