The objective of this research was to clarify the potential impacts of propolis and its nanoparticles in protecting an edible and economically significant tilapian fish, Oreochromis niloticus in Egypt after feeding M. aeruginosa cells mixed with their food on biochemical variables and histopathological changes of liver under laboratory conditions. The results showed that the diet containing M. aeruginosa cells caused aspartate transferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), creatinine and urea to increase significantly compared to the control groups. Various histopathological modifications were noted in the liver tissues which were described by marked degenerative changes within the hepatic and pancreatic portion. Whereas propolis and nanopropolis co-administration causes these parameters to significantly decrease with best result for nanopropolis. The study concluded that the uptake of M. aeruginosa orally had deleterious impacts on some clinical and biochemical parameters of the blood of Nile tilapia that ultimately impacted the health of fish. The current findings evoked that the administration of propolis and its nanoparticles increases fish health and soothes M. aeruginosa induced toxicity. Nano form of propolis is more efficient in competing toxicity of m. aeruginosa and as hepatoprotective agent.