Poly(beta-hydroxybutyrate) (PHB) thermoplastics hold appeal for many applications due to their high biodegradability compared to petrochemical-based plastics. PHB is currently produced using fermentation technologies and purification techniques that have considerable potential for optimization. Current PHB production methods require impractical amounts of organic solvents for the removal of residual fermentation media necessary for medical utility. We conceptualized an alternative process using high-pressure CO2 as an alternative solvent for PHB purification. The extraction of plant oil residues that are the main contaminants in PHB produced by fermentation were compared under conditions of varying pressure, temperature, and co-solvents. Using pure CO2 at 150 bar and 50 degrees C achieved the removal of 73 +/- 5 wt% of oil residue, and this was increased to 93 +/- 3 wt% using an ethanol CO2 expanded solution. This novel approach to the purification of PHB will enable further developments of PHB thermoplastics for biomedical applications.