► PtPd and PtIr NPs-decorated multiwalled carbon nanotube nanocatalysts (PtM/MWCNTs) were prepared by a modified Watanabe method. ► PtPd/MWCNTs/GC electrode exhibited a low detection limit of 1.2μM. ► PtPd/MWCNTs/GC electrode with a wide linear range of 2.5–125μM (R2=0.9996). ► A low working potential (0.25V (SCE)), high sensitivity (414.8μAmM−1cm−2) were achieved the PtPd/MWCNTs/GCE. A new highly catalytic and intensely sensitive amperometric sensor based on PtM (where M=Pd, Ir) bimetallic nanoparticles (NPs) for the rapid and accurate estimation of hydrogen peroxide (H2O2) by electrooxidation in physiological conditions is reported. PtPd and PtIr NPs-decorated multiwalled carbon nanotube nanocatalysts (PtM/MWCNTs) were prepared by a modified Watanabe method, and were characterized by XRD, TEM, ICP, and XAS. The sensors were constructed by immobilizing PtM/MWCNTs nanocatalysts in a Nafion film on a glassy carbon electrode. Both PtPd/MWCNTs and PtIr/MWCNTs assemblies catalyzed the electrochemical oxidation of H2O2. Cyclic voltammetry characterization measurements revealed that both the PtM (M=Pd, Ir)/MWCNTs/GCE possessed similar electrochemical surface areas (∼0.55cm2), and electron transfer rate constants (∼1.23×10−3cms−1); however, the PtPd sensor showed a better performance in H2O2 sensing than did the PtIr counterpart. Explanations were sought from XAS measurements to explain the reasons for differences in sensor activity. When applied to the electrochemical detection of H2O2, the PtPd/MWCNTs/GC electrode exhibited a low detection limit of 1.2μM with a wide linear range of 2.5–125μM (R2=0.9996). A low working potential (0V (SCE)), fast amperometric response (<5s), and high sensitivity (414.8μAmM−1cm−2) were achieved at the PtPd/MWCNTs/GC electrode. In addition, the PtPd/MWCNTs nanocatalyst sensor electrode also exhibited excellent reproducibility and stability. Along with these attractive features, the sensor electrode also displayed very high specificity to H2O2 with complete elimination of interference from UA, AA, AAP and glucose.