Precise selectivity and rapid responses to target biomolecules are important in the development of biosensors. In particular, highly sensitive and selective biosensors have been used in clinical treatment to detect factors such as cancer oncoproteins and endocrine disruptors. Herein, highly sensitive liquid electrolyte field-effect transistor (FET) system biosensors were fabricated to detect platelet-derived growth factor (PDGF) using a PDGF-B binding aptamer conjugated with carboxylic polypyrrole-coated metal oxide-decorated carbon nanofibers (CPMCNFs) as the signal transducer. First, CPMCNFs were fabricated using vapor deposition polymerization (VDP) of the carboxylic pryrrole monomer (CPy) on metal oxide-decorated carbon nanofiber (MCNF) surfaces with no treatment for carbon surface functionalization. Furthermore, a 3 nm thick uniformly coated carboxylic polypyrrole (CPPy) layer was formed without aggregation. The CPMCNFs were integrated with the PDGF-B binding aptamer and immobilized on the interdigitated array substrate by covalent anchoring to produce a FET-type biosensor transducer. The PDGF-B binding aptamer conjugated CPMCNF (CPB-Apt) FET sensor was highly sensitive (5 fM) and extremely selective for isoforms of PDGFs. Additionally, the CPB-Apt FET sensor could be reused over a few weeks.