Mass photometry (MP) enables rapid, high-resolution analysis of mRNA integrity and purity under native conditions. It provides single-molecule, quantitative measurements of full-length transcripts, degraded fragments, and aggregates within minutes. Here, three commercial GFP mRNAs were assessed under native conditions, during thermal refolding and denaturation, and during forced degradation. The results highlight MP’s ability to directly quantify mRNA integrity under stress, providing crucial insights into how mRNA design and formulation influence overall stability.