This study aims to investigate the effects of plasma exchange on the biomolecular profiles and histology of ileum and colon tissues in young and aged Sprague–Dawley male rats. Fourier transform infrared (FTIR) spectroscopy, linear discriminant analysis and support vector machine (SVM) techniques were employed to analyse the lipid, protein, and nucleic acid indices in young and aged rats. Following the application of young plasma, aged rats demonstrated biomolecular profiles similar to those of their younger counterparts. Histopathological and immunohistochemical assessments showed that young plasma had a protective effect on the intestinal tissues of aged rats, increasing cell density and reducing inflammation. Additionally, the expression levels of key inflammatory mediators tumour necrosis factor‐alpha and cyclooxygenase‐2 significantly decreased after young plasma administration. These findings underscore the therapeutic potential of young plasma for mitigating age‐related changes and inflammation in the intestinal tract. They highlight the critical role of plasma composition in the ageing process and suggest the need for further research to explore how different regions of the intestines respond to plasma exchange. Such understanding could facilitate the development of innovative therapies targeting the gastrointestinal system, enhancing overall health during ageing.