The present study focuses on the nanoparticle interaction with human peripheral blood cells from genetic and ultra structure study. AgNPsgenotoxicity and cytotoxicity had been tested in human peripheral blood lymphocytes culture through DNA fragmentation, chromosomal aberrations and electron microscope. Also, metal ion analysis was done to check the uptake of nanoparticles in the cell pellet of human peripheral blood cells. AgNPs proved to be genotoxic in human peripheral blood lymphocytes culture through the fragmentation of DNA, chromosomal aberrations and metal ion analysis. Aberrant cell damage was recorded to be 0, 8 and 24% for 5, 15 and 25μg/mL of AgNPs respectively. Significant increase and decrease in CAs and MI, respectively. Marked alterations in the ultrastructure blood cells in the form of: apoptosis of leukocytes and destruction of erythrocytes membrane. Structural changes in chromosomes and chromatids were also recorded. AgNPs was found to be cytotoxic and genotoxic.