The purpose of the present study was to assess the nutritional value of yeast culture (YC) and to explore the effect of YC on growth performance and health of piglets fed low-protein (LP) diets. In Exp.1, 12 growing barrows were allocated into control diet and YC diet treatments to determine the available energy of YC. Results showed that the digestible energy and metabolizable energy of YC are 12.12 and 11.66 MJ/kg dry matter (DM), respectively. In Exp.2, 12 growing barrows were surgically equipped with a T-cannula near the distal ileum and were assigned to 2 dietary treatments (nitrogen-free diet and YC diet), and the amino acid digestibility of YC was determined. In Exp.3, a total of 96 weaned piglets were randomly divided into 4 treatments, including LP basal diet (Basal), Basal+0.5% YC (0.5%YC), Basal+1.0% YC (1%YC), and Basal+1.5% YC (1.5%YC). The results were as follows: YC supplementation linearly improved the weight gain and feed intake ratio (P < 0.001), linearly increased the activity of glutathione peroxidase on d 14 (P = 0.032) and linearly decreased the concentration of malondialdehyde on d 14 (P = 0.008) and d 32 (P = 0.004) in serum, and linearly decreased the concentration of total short-chain fatty acid on d 14 in feces (P = 0.045). Compared with other treatments, 1.5%YC group showed a greater abundance of various probiotics, such as Prevotellaceae, Prevotella and Turicibacter. In Exp.4, twelve growing barrows with an ileal T-cannula were randomly assigned to Control and 1.5%YC treatments to clarify the impact of YC supplementation on nitrogen balance and nutrient digestibility. Results showed that YC had no significant effect on nitrogen efficiency and nutrient digestibility, except for trend of reducing the total tract digestibility of organic matter (P = 0.067). In conclusion, the present study assessed the digestible and metabolizable energy values (12.12 and 11.66 MJ/kg DM, respectively) and standardized ileal digestibility of amino acid (from 43.93% to 82.65%) of YC in pig feed and demonstrated that moderate supplementation of YC (1.5% of diet) can effectively improve feed conversion efficiency, enhance antioxidant capacity, and promote a balanced gut microbiota in piglets.