Millions of tons of crab shells are annually discarded. Crab shells contain several valuable compounds such as chitosan that can be transformed into chitosan nanomaterials. The unique properties and applications of nanotechnology in targeting fish processing technology have received increased importance during the last twenty years. The application of nanotechnology in fishery products is rapidly increasing, and investigating the toxicity and safety of these nanoparticles is essential before their nutritional use. Therefore, this study aimed to determine the acute and chronic toxicity of crab chitosan and its nanoparticles (ChNPs) on albino mice and sprague Dawley rats, respectively. Acute toxicity revealed that crab chitosan and chitosan nanoparticles were completely safe up to 10g/ kg of mice body weight which is equivalent to 38.75g/ 70kg of man body weight, as there was no mortality among used mice.  Chronic toxicity testing using 200mg/ kg crab chitosan and 100 & 200mg/ kg chitosan nanoparticles revealed no changes in all the assayed biochemical parameters when compared with those of control rats. No changes were detected in the lipid profile (T-Ch, TG, HDL-Ch& LDL-Ch) of rats given chitosan in normal and nano form in comparison with normal rats. Levels of plasma protein, albumin, globulin and A/G ratio showed no significant differences among different groups. Normal levels of kidney functions (creatinine & urea) and liver enzymes (ALT & AST) for all studied groups were obtained compared to normal rats. Histopathological examinations of liver sections showed nearly normal appearance in all studied groups. In conclusion, the prepared crab chitosan nanoparticles can be added to the non-toxic (safe) class of materials. It seemed to be an upcoming product that can be used safely as food additives.