This study aimed to determine the optimal depuration strategy for largemouth bass (Micropterus salmoides) by examining the effects of varying treatment times and stocking density on phenotypic characteristics, health status, and muscle nutritional quality. M. salmoides with an initial body mass of (460.60±12.74) g were used as the research object. Three stocking densities (2.5, 7.5 and 12.5 kg/m³) were established, and two feeding modes were combined: short-term depuration (7 d, non-feeding) and long-term starvation (28 d, small-scale feeding). The results showed that, compared with the control (0 d), the hepatosomatic index (HSI), visceral index (VSI), and saturated fatty acid (SFA) content in muscle decreased significantly after depuration, while the condition factor (CF) and the proportion of essential amino acids (EAA/TAA) in muscle increased significantly. The content of essential amino acids (EAA), amino acid score (AAS), and essential amino acid index (EAAI) generally increased with the extension of net rearing time. Compared to short-term depuration (7 d), the body weight, CF, and total blood protein content (TP) of fish increased significantly after long-term depuration (28 d), while VSI and blood low-density lipoprotein cholesterol (LDL-C) content decreased significantly. Furthermore, comparisons among different density groups revealed that HSI, VSI, blood glucose (GLU), and LDL-C content, as well as muscle SFA content, decreased with increasing breeding density. In contrast, blood biochemical indexes, liver superoxide dismutase (SOD) content, and muscle crude protein, ash, and total essential amino acids (TAA) generally exhibited the highest values in the medium stocking density (MSD) group. Overall, long-term depuration can lead to greater consumption of visceral fat, improved fish body shape characteristics, and enhanced nutritional quality of fish muscle. Therefore, the optimal depuration strategy for M. salmoides is 28 d depuration with small amounts feeding at stocking density of 7.5 kg/m³. This study provides a theoretical reference for the application and popularization of ecological depuration culture model of M. salmoides.