The present study investigated the effects of dietary Edwardsiella tarda (E. tarda) specific bacteriophage (phage) and Bacillus subtilis (B. subtilis) mixture on innate immune responses and antibacterial activity of Nile tilapia, Oreochromis niloticus. In a dietary experiment, tilapia were fed the control diet (C), a phage-only supplemented diet (P), a B. subtilis only supplemented diet (B), or a B. subtilis and phage mixed diet (B+P). A respiratory burst and significant increase in lysozyme activity (P<0.05) were noted in the B+P group, as compared to other groups after 4 days of feeding. The B group showed a significant (P<0.05) increase in respiratory burst and lysozyme activity versus the C and P groups, whereas no significant increases (P<0.05) were observed in the P and C groups. $ACH_{50}$ was significantly up-regulated in the B+P group versus other groups after 8 days of feeding (P<0.05). In vivo antibacterial activity was significantly enhanced in the B+P fed group, as compared to other groups (P<0.05) after 7 days of E. tarda challenge. A significant (P<0.05) increase in antibacterial activity was seen in the B group, as compared to C or P groups after 14 days of feeding. These results suggest that a B. subtilis and phage mixture could be utilized as an alternative to antibiotics in the control of fish diseases caused by E. tarda.