The antimicrobial efficacy of novel photodynamic inactivation and nanobubble technologies was evaluated against Vibrio parahaemolyticus and Aeromonas hydrophila as two important aquatic microbial pathogens. Photodynamic inactivation results showed that LED (470 nm) and UV-A (400 nm)-activated curcumin caused a complete reduction in V. parahaemolyticus at 4 and 22 °C, and a greater than 2 log cfu/mL reduction in A. hydrophila, which was curcumin concentration-dependent (p < 0.05). Furthermore, the photodynamic approach caused a greater than 6 log cfu/mL V. parahaemolyticus reduction and more than 4 log cfu/mL of A. hydrophila reduction in aquaponic water samples (p < 0.05). Our results with the nanobubble technology showed that the nanobubbles alone did not significantly reduce bacteria (p > 0.05). However, a greater than 6 log cfu/mL A. hydrophila reduction and a greater than 3 log cfu/mL of V. parahaemolyticus reduction were achieved when nanobubble technology was combined with ultrasound (p < 0.05). The findings described in this study illustrate the potential of applying photodynamic inactivation and nanobubble–ultrasound antimicrobial approaches as alternative novel methods for inactivating fish and shellfish pathogens.