Super large proteinaceous particles (SLPPs) such as virus, virus like particles, and extracellular vesicles have successful and promising applications in vaccination, gene therapy, and cancer treatment. The unstable nature, the complex particulate structure and composition are challenges for their manufacturing and applications. Rational design of the processing should be built on the basis of fully understanding the characteristics of these bio‐particles. This review highlights useful analytical techniques for characterization and stabilization of SLPPs in the process development and product formulations, including high performance size exclusion chromatography, multi‐angle laser light scattering, asymmetrical flow field‐flow fractionation, nanoparticle tracking analysis, CZE, differential scanning calorimetry, differential scanning fluorescence, isothermal titration calorimetry , and dual polarization interferometry. These advanced analytical techniques will be helpful in obtaining deep insight into the mechanism related to denaturation of SLPPs, and more importantly, in seeking solutions to preserve their biological functions against deactivation or denaturation. Combination of different physicochemical techniques, and correlation with in vitro or in vivo biological activity analyses, are considered to be the future trend of development in order to guarantee a high quality, safety, and efficacy of SLPPs.