Recently, hybrid biocatalysts with a unique interfacial structure have attracted significant attention for enzyme mimicking due to their superior catalytic activity compared with the single component catalyst. In this work, novel sheet-on-tube heterostructured polypyrrole (PPy)@CoO/NiO nanotubes (NTs) are synthesized via an in situ growth strategy and are utilized for enzyme mimicking and sensing applications. The as-prepared PPy@CoO/NiO NTs can catalyze H2O2 into ·OH and realize the 3,3′,5,5′-tetramethylbenzidine (TMB) oxidation, showing an excellent peroxidase-like property. Thanks to the synergistic effect between PPy NTs and CoO/NiO nanosheets, the catalytic performance of the resultant PPy@CoO/NiO NTs is superior to individual PPy NTs and bare CoO/NiO sheets as well as their physical mixture. In addition, the PPy@CoO/NiO NTs can also catalyze the H2O2 decomposing to generate O2, possessing a catalase-like property. Then, we perform a simple visual method for sensitively detecting H2O2 and ascorbic acid (AA). This work demonstrates a distinctive route to promote the catalytic performance of enzyme-like nanomaterials for huge potentials in biotechnology and environment fields.