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Objective: To evaluate the use of protein glycation inhibitors and probiotics to ameliorate secondary complications in diabetes and to improve gut microbiota respectively in high fructose fed Wistar rat. Methods:The study was conducted on male Wistar rats for 7 d. Blood glucose levels in oral glucose tolerance test (OGTT) were measured using glucometer, serum parameters were analyzed using commercial kits, antioxidant status was evaluated by measuring superoxide dismutase (SOD) and catalase (CAT) levels, total reactive oxygen species were estimated using a fluorescent 2', 7'-dichlorofluorescin diacetate (DCF-DA) dye, and tissue fluorescence of liver, kidney and intestine were measured using a spectrofluorimeter.Results: OGTT pattern shows significant increase in blood glucose of fructose fed rats i.e. 154 mg/dl while, in aminoguanidine (AMG) treated and gut microbiota modulated animals it is 137 and 119 mg/dl resp. after 30 min on glucose administration. Marked reduction was found in SOD 6.37 and 11.25 U/mg of protein and catalase 186 and 65.5 U/mg of protein in liver and kidney of fructose fed animals when compared to fructose+AMG and fructose+EUGI. There is 5-6 fold significant increase in general and specific tissue fluorescence of liver and kidney, and 2.2 fold increase in liver reactive oxygen species was observed in fructose fed group as compare to control animals. Significantly higher glycation was found in intestine of fructose fed animals (general fluorescence 2.1 and specific fluorescence 3.1 AU/mg), more than that of diabetic control rats (general fluorescence 0.9 and specific fluorescence 1.6 AU/mg), represented an evidence for adverse impact of excess fructose on healthy gut. Conclusion:The use of protein glycation inhibitor and use of pre and probiotics significantly improved the serum parameters and would prevent progression to secondary complications.