Background: Propolis is a complex resinous mixture that is gathered and processed by honeybees from resin they collect from trees and plants. This substance has various biological properties. Glycation is a reaction, which occurs between a protein and a reducing sugar and finally causes structural alterations and destruction of proteins. The role of glycation has been approved in the development and aggravation of diabetic complications. This study aimed to examine the effect of ethanolic extract of propolis (EEP) on fructation and destruction of hemoglobin protein structure. Materials and Methods: In this experimental study, purified hemoglobin was incubated alone and with fructose in the presence and absence of different concentrations of EEP (10, 20 and 40µg/ml) for 5 weeks. The extent of hemoglobin fructation was determined by measuring the amount of heme release, blue shift in soret band, releasing the products of heme destruction and assessing the amyloid structures using the UV-visible and fluorescence spectroscopy. Results: Incubation of hemoglobin with fructose was led to the hemoglobin destruction and heme release. Hemoglobin fructation was inhibited up to 45 in the presence of EEP with a concentration of 40µg/ml. The two lower concentrations of EEP showed the lower degrees of inhibition. Moreover, fluorescence studies of products resulting from heme degradation and fibrillar structures are indicative of the reduction in hemoglobin fructation in the presence of EEP. Conclusion: Hemoglobin is drastically glycated in the presence of fructose and EEP can decrease the hemoglobin fructation in a concentration-dependent manner