Background Mefenamic Acid (MFA) is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a short-term treatment for mild to moderate pain and inflammation. However, like many other NSAIDs, MFA has been widely associated with many adverse effects such as hepatotoxicity, neurotoxicity, increasing risks of inflammation, causing damage to the mucosal lining, gastrointestinal lesions, among many other harmful effects.This study aimed to prepare a prodrug of mefenamic acid: Hydroxyethyl Ester of Mefenamic Acid (HEMA), intending to examine whether it can potentially counteract some of the adverse effects MFA, including central nervous system toxicity, as well as its potential to improve the efficacy of MFA. Methodology This study uses an experimental approach adopted from a stepwise procedural protocol to synthesise and prepare HEMA, administered to a sample of 168 male mice for observation. Four experimental tests are used to determine the effects of administering HEMA to the sample, which include: (1) Acute Toxicity Test, (2) Carrageenan-Induced Paw Edema Test, (3) Acetic Acid-Induced Visceral Pain Test, and (4) Formalin Induced Licking Test. Analysis of Variance (ANOVA) and Tukey tests are used to statistically analyse the experimental tests' findings. Results The findings of the Acute Toxicity Test showed that the mice group treated with HEMA showed significantly reduced effects in comparison to the group treated with MFA exemplified through: (1) significantly lower grimace scores, (2) decreases in locomotor activity, (3) suffered from fewer instances of catalepsy and seizures, and (4) showed reduced mortality percentages during the 14 days of the experiment. The findings of the Acetic Acid-Induced Writhing Response Test and Carrageenan Induced Hind Paw Edema Test showed significant positive differences in criteria between the treatment groups. Conclusions Overall, the findings of This study suggest that HEMA is a promising prodrug substitute for MFA, reducing adverse effects and enhancing the drug's efficacy. Keywords Mefenamic Acid; Hydroxyethyl Ester of Mefenamic Acid; HEMA; Experimental; Mice; Acute Toxicity Test; Carrageenan-Induced Paw Edema Test; Acetic Acid-Induced Visceral Pain Test; Formalin Induced Licking Test