Establishing the toxicity and exposure consequences of microplastics (MPs) on marine organisms relies on the nondestructive isolation of plastics from biological matrices. MPs are commonly extracted from these matrices by chemical digestion using alkali (e.g., potassium hydroxide (KOH) and sodium hydroxide (NaOH)), oxidative (e.g., hydrogen peroxide (H 2 O 2 )) and/or acidic (e.g., nitric acid (HNO 3 )) reagents. Although these digestion conditions can be highly effective for MP extraction, they can also react with the plastics. This can attribute an inaccurate representation of plastic contamination by altering MP visual characteristics (size, shape, color), thereby impeding identification and potentially returning erroneous numbers of ingested particles. In this study, the degradative impacts are assessed of the routinely applied digestion reagents (i) KOH, (ii) NaOH, (iii) H 2 O 2 , and (iv) HNO 3 on polystyrene (PS) based MPs sized between 200 μm and 5 mm. Degradation of the PS MPs is evaluated using FT-IR, gel permeation chromatography, NMR, photoluminescence spectroscopy, and microscopy. These studies reveal HNO 3 to be the most destructive for PS MPs, while the alkali and oxidative reagents result in negligible changes in plastic properties. These results are recommended to be used as a guideline to update current protocols to ensure the nondestructive treatment of MPs.