Given the role of oxidative damage in the development and progression of diabetic complications, the potential antioxidant activity of erythritol has been investigated in both in vitro and in vivo studies [15]. The current literature indicates that erythroid is easily absorbed, does not undergo systemic metabolism, and is rapidly excreted without undergoing any changes in the urine [16]. [PERSON] et al. [17] conducted a study on the effects of erythroid on glucose metabolism and oxidative stress in diabetic rats. The results showed that erythroid had a positive impact on lowering the serum glucose levels by up to 15% at the highest dose, as well as in hepatic and renal tissues. Erythritol was also found to be an effective hydroxyl radical scavenger and inhibitor of diazo compound-induced erythrocyte damage in vitro. In diabetic rats, erythritol consumption did not affect the endothelial function and was accompanied by the presence of erythroid metabolites with antioxidant properties in the urine. These findings suggest that erythritol acts as an antioxidant in vivo and may help protect against vascular damage induced by hyperglycemia. Unlike other polyols that often cause digestive issues, erythroid is highly tolerated by the body. Research indicates that at typical consumption levels, erythroid does not cause a laxative effect. Its small molecular size plays a crucial role in its high level of digestive tolerance, allowing it to be rapidly absorbed into the upper digestive tract. As a result, only minimal amounts reach the lower digestive tract, where the degradation of polyols and osmotic effects typically lead to gastric discomfort. For the synthesis of the ibuprofen esters, we decided to embark on the path of chemical modifications mediated by pathways with biological origins, also called biotransformation. These biochemical transformations can be achieved by exploiting whole cells (bacteria [18] or fungi [19]), their lysate, or isolated enzymes [20]. The latter allows for the synthesis of prodrugs through straightforward synthetic pathways, characterized as cheaper, less energy-consuming, and more selective compared to the canonical chemical modifications. Thus, among the reactions that can be carried out with these biotransormative processes, esterification reactions represent green methods for the synthesis of active ingredient derivatives. For this purpose, lipases, specifically triacylglycerglycerol hydrolases (EC 3.1.1.3), are extensively utilized for biocatalytic esterification reactions. They act as the main biocatalysts in enzymatic esterification processes. Indeed, since the 1990s, lipases have facilitated researchers and industries in the synthesis of ester bonds under mild reaction conditions, with no need for co-factors, while displaying stereo-specificities towards a wide range of substrates. Nowadays, green processes are the key step to achieve goals with a controlled and aware environmental impact. Moreover, the exploitation of green chemistry can also provide new ways to achieve goals that cannot be achieved with the traditional pathways. By exploiting enzymes, is it possible to attain products with specificity and purity that cannot be reached with chemical synthesis [21]. This article reports the study of a biocatalytic approach for producing prodrugs enhanced in water solubility. With this aim, ibuprofen was chosen as the target active principle, and erythroid as the hydrophilization moiety. Along with the study, the enantioselective esterification of ibuprofen with glycerol is also reported.