Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG) triphenylphosphonium (TPP) conjugate (i.e., mPEG (ss-TPP)(2) conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG (ss-TPP)(2) self-assembled in aqueous media, which thereby formed core shell structured nano particles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG (ss-TPP)(2) NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG (ss-TPP)(2) NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.