Polypyrrole (PPy) is most widely used conductive polymer for conductive textile applications owing to its excellent electrical conductivity, good electromagnetic shielding, good anti-bacterial properties, etc. However, it has not been explored much as thermoelectric material. PPy can be coated on cotton fabric in aqueous media from its monomer to prepare electro-conductive fabrics, which will be a flexible organic thermoelectric material. In this study, PPy-coated cotton fabrics are prepared by in situ chemical polymerisations of pyrrole in presence of ferric chloride. The polymerisation process is optimised by employing Box–Behnken response surface design and method of steepest ascent to achieve minimum electrical resistivity. The lowest resistivity of PPy-coated cotton fabric is achieved to be 1.23 Ω/cm after the optimisation. The PPy-coated cotton fabric with copper thermocouple shows Seebeck coefficient as high as 11.95 µV/K, power factor 0.139 µW m−1 K−2, and thermoelectric figure of merit 1.22 × 10−4 at an absolute temperature of 300K. The thermoelectric performance of this coated fabric is found to be comparable to other costly conductive polymers and inorganic semiconductors. The surface morphology of PPy-coated cotton fabric is observed by field-emission scanning electron microscopy. Chemical interaction between cotton and PPy is investigated by FTIR spectroscopy. Analysis of semi-crystalline structure is done by X-ray diffraction and thermo-gravimetric analyser is used for analysis of thermal degradation.