Probiotics and prebiotics are increasingly encouraged in aquaculture to reduce antibiotic use. The present study aimed to investigate the effects of dietary supplementation of peptidoglycan or Lactobacillus plantarum or its combination on the growth performance, disease resistance, and immune status of striped catfish juvenile. Fish were fed on the commercial feed supplemented with various concentrations of peptidoglycan and Lactobacillus plantarum at 0, 5, 5, 2.5 + 2.5, and 5.0 + 5.0 per kg of feed, named to PP0.0, PG5.0, LP5.0, PP2.5, and PP5.0 treatments. Fish were then fed at a ration of 3% of fish body weight for 6 weeks. After feeding trial, fish were infected with Aeromonas veronii at 50% lethal dose (LD50, 107 CFU/mL). Blood samples were collected after 2, 4, and 6 weeks of experiment (T2, T4, and T6) and at second day after bacterial infection for hematological parameters and immune assays. The results demonstrated that supplementation with PP2.5 significantly improved growth performance and feed utilization in fish, while the LP5.0-based diet reduced mortality in A.veronii-challenged fish, indicating enhanced disease resistance. The modifications in hematology and immune status were affected by pro-, pre-, and synbiotics tested in this study. In conclusion, dietary supplementation with peptidoglycan and L.plantarum enhances growth, immunity, and disease resistance in striped catfish, supporting sustainable aquaculture practices for improved fish health and production efficiency.