Human erythrocytes or red blood cells (RBCs), which constitute 99% of blood cells, perform an important function of oxygen transport and can be exposed to nanoparticles (NPs) entering into the human body during therapeutical applications involving such NPs. Hence, the haemocompatibility of the Ag, Au, and Pt NPs on human RBCs is investigated. The parameters monitored include haemolysis, haemagglutination, erythrocyte sedimentation rate, membrane topography, and lipid peroxidation. The findings suggest that platinum and gold NPs are haemocompatible compared to Ag NPs. Erythrocytes exhibit significant lysis, haemagglutination, membrane damage, detrimental morphological variation, and cytoskeletal distortions following exposure to Ag NPs at a concentration of 100 µg mL−1. Exposure of Ag+ to RBCs shows no lysis or deterioration, implying that the observed toxicity is solely due to NPs. The haemolyzed erythrocyte fraction has the ability to induce DNA damage in nucleated cells. Additionally, multiple pits and depressions are observed on RBC membrane following exposure to Ag NPs (50 µg mL−1 onwards). Hence, it is apparent that Ag NPs exhibit toxicity on RBCs and on other cells that are exposed to NP-mediated haemolyzed fractions.