Display omitted •Green synthesis of a nanocomposite consisting of poly(3,4-ethylenedioxythiophene) and ZrO2 nanoparticles was developed.•The nanocomposite possesses good conductivity and a three-dimensional microporous network structure.•The PEDOT/ZrO2-NPs/GCE exhibits excellent electrocatalytic activity towards oxidation of progesterone.•The proposed sensor was successfully applied for the determination of progesterone in biological fluids and pharmaceuticals. The present study describes a green synthesisof a nanocomposite consisting of poly(3,4-ethylenedioxythiophene) and zirconium oxide nanoparticles. The nanocomposite possesses good conductivity and a three-dimensional microporous network structure owing to the presence of the nanoparticles. Data from the scanning electron microscopy, field-emission scanning electron microscopy, energy dispersive spectrum and Fourier transform infrared spectroscopy demonstrated that the proposed nanocomposite was successfully synthesized. A glassy carbon electrode modified with the nanocomposite exhibits excellent electrocatalytic activity towards oxidation of progesterone. Some parameters affecting the sensor response were optimized and then the calibration curve was plotted. The detection limit of 0.32 nM and two linear calibration ranges of 1–100 and 100–6 × 103 nM were obtained for progesterone determination at the proposed sensor. It was successfully applied for the determination of progesterone in biological fluids and pharmaceutical products without complex sample pretreatment.