<p>Background: Protein aggregation is one of the important, common and troubling problems in biotechnology, pharmaceutical industries and amyloid-related disorders.<br /> Methods: In the present study, the inhibitory effects of some carbohydrates (alginate, &beta;-cyclodextrin and trehalose) on the formation of nano-globular aggregates from normal (HSA) and glycated (GHSA) human serum albumin were studied; when the formation of aggregates was induced by the simultaneous heating and addition of dithiotheritol. For the investigations, the biophysical methods of UV-vis spectrophotometry, circular dichroism spectroscopy, transmission electron microscopy and tensiometry were employed.<br /> Results: The effect of inhibitory mechanism of these inhibitors on the aggregation of HSA and GHSA was expressed and compared together.<br /> Conclusion: The results showed that the nucleus formation step of the aggregation process of HSA and GHSA was different in the presence of alginate (compared to &beta;-cyclodextrin and trehalose). The inhibition efficiencies of the carbohydrates on the aggregate formation of HSA and GHSA were different, arising from the differences in the hydrophobicities of HSA and GHSA, and also, the differences between HSA- and GHSA-carbohydrate interactions.</p>