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Rheumatoid arthritis (RA), a chronic inflammatory disease, and its exact aetiology is not defined clearly. The free radicals produced in large amount in RA are associated with alteration in molecular structure resulting in glycation of proteins. As a result of glycation, advanced glycation end products (AGEs) produced. In this study, collagen type II suspension was injected into Wistar rats to make RA model of rats. Simultaneously, hesperidin 50 mg kg -1 body weight was orally administrated to the rats for 21 days. X-rays of the rat hind paws were analyzed and found to be significantly effective against bone loss after treatment with hesperindin. N ε -(carboxymethyl)lysine (CML) and pentosidine (PTD) concentrations in collagen-induced RA plasma were determined as 565.29 ± 30.15 and 37.23 ± 1.02 ng ml -1 , respectively, while CML and PTD in IgG were 6.63 ± 0.44 ng mg -1 IgG and 425.33 ± 37.26 ng g -1 IgG, respectively. After treatment with hesperidin, the elevated levels of CML in plasma and in IgG were significantly (p < 0.001) lowered to 450.95 ± 15.05 mg ml -1 and 5.23 ± 0.27 ng mg -1 IgG, respectively. Similarly, concentrations of PTD in plasma and IgG of rats treated with hesperidin were 28.46 ± 1.20 ng ml -1 and 359.35 ± 31.11 ng g -1 IgG, respectively. Thus, after treatment with drug, plasma CML and IgG PTD levels were restored as 93% and 16%, respectively, through free radical scavenging activity of hesperidin resulting in alleviation of RA disease by decreasing the AGEs concentrations. Therefore, use of hesperidin may be useful to alleviate severity of RA disease., (© 2022 John Wiley & Sons Ltd.)