The gastrointestinal adverse effects of NSAIDs can be mitigated and the therapeutic efficacy enhanced through carboxyl group modification. The selection of naproxen and mefenamic acid, both anti-inflammatory medications, was made with the purpose of developing mutual prodrugs in combination with paracetamol. The chemicals were produced with the objective of attaining a synergistic outcome and mitigating the stomach irritation associated with nonsteroidal anti-inflammatory drugs (NSAIDs). The compounds were verified using the process of spectrum characterisation. The experimental procedure encompassed the esterification reaction between the carboxyl functional group of specific nonsteroidal anti-inflammatory drugs (NSAIDs) and the hydroxyl functional group of paracetamol. The hydrolysis research of mutual prodrugs was conducted in both an acidic medium and a phosphate buffer. The study determined that compounds exhibit regulated hydrolysis in the environment. Consequently, it was concluded that a mutual prodrug strategy can be successfully employed to enhance the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in two distinct manners. The first involves masking the carboxyl group of NSAIDs, while the second strategy involves utilizing paracetamol as a pro moiety to achieve synergistic effects. The mutual prodrugs have demonstrated the ability to maintain their anti-inflammatory properties while significantly reducing gastrointestinal irritation.