In this study, multiwalled carbon nanotube@reduced graphene oxide nanoribbon (MWCNT@rGONR) core-shell heterostructures have been synthesized by the facile unzipping of MWCNTs and subsequent chemical reduction with hydrazine. MWCNTs with diameter <10 nm were selected as the starting material to maintain narrow ribbons <30 nm wide with a few-layer structure. The most important discovery is that the resulting MWCNT@rGONR heterostructures possess intrinsic peroxidase-like activity, 15.9 times higher than that of MWCNTs and 8.4 times higher than that of their unreduced form. The nature of the peroxidase-like activity of the MWCNT@rGONR heterostructures can be attributed to the acceleration of their electron-transfer process and the consequent facilitation of ˙OH radical generation. Kinetic analysis demonstrates that the catalytic behavior is in accordance with typical Michaelis-Menten kinetics and the obtained kinetic parameters indicate that the MWCNT@rGONR heterostructures display a higher affinity for both H2O2 and 3,3,5,5-tetramethylbenzidine than that of horseradish peroxidase. On this basis, we have employed the MWCNT@rGONR heterostructures as novel biosensing platforms to develop a simple, sensitive, and selective colorimetric biosensor for free cholesterol determination. This work will facilitate the formation of MWCNT@rGONR heterostructures with narrow ribbons and the utilization of their intrinsic peroxidase-like activity in biotechnology and medical diagnostics.