The therapeutic potential of methanolic extract, pectin, hesperidin, and naringin derived from Citrus paradisi peel (grapefruit) was investigated against the toxicity of silver nanoparticles (AgNPs). Mice received orally AgNPs of size 20 &100nm for four weeks then treated with methanolic extract, pectin, hesperidin, and naringin for three weeks. C. paradisi peel yielded methanolic extract (11.37%), pectin (30.88%), naringin (4.3%) and hesperidin (0.09%),the results showed a significant reduction in lung tissue ;Adenosine triphosphate ,Adenosine diphosphate and Adenosine monophosphate respectively (ATP, ADP, AMP), total adenylate (TA), inorganic phosphate (IP), phosphate potential (PP), and adenylate Energy Charge (AEC). Besides, obvious decrease in both vitamin E and C levels in both sizes of Ag–intoxicated, along with marked inhibition in superoxide dismutase (SOD) and catalase antioxidant enzyme activities. While oxidative stress markers; MDA was significantly elevated. More severe damage was detected with a smaller size of 20 nm than 100 nm AgNPs particle size compared to the control mice. Histopathological examination revealed inflammation and cellular degeneration caused by AgNPs after, treatment with the above compounds showing repair ease. C. paradisi derived by products including phenolic extract, pectin, hesperidin, and naringin that are handled unexpectedly as promising competitor remedial specialists against poisonousness induced by AgNPs in mice.