A screening protocol was developed and implemented to evaluate extremophiles, in particular hyperthermophiles and thermoacidophiles, for their capacity to transform starch-based feedstocks to high-value organic acids and solvents. Screening results of 14 extremophiles showed promising growth and biotransformation potentials. In particular, Hyperthermus butylicus, Thermococcus litoralis, and Sulfolobus acidocaldarius were identified as producers of both organic acids and solvents under the screening protocol. The screening effort presented here represents an important step toward realization of biotransformation potentials of extremophiles, potentially improving upon biomass-based processes.