Eugenol is acknowledged as a potent anti-inflammatory and analgesic agent. Due to the opacity for the development of effective and affordable topical pharmaceuticals and lack of a multi-mechanistic approach, the present study is aimed to develop a eugenol-based topical formulation and explore the multi-mechanistic effect of eugenol-based gel formulation for analgesic and anti-inflammatory action. Pre-formulation and post formulation studies were conducted to evaluate the drug compatibility with certain bases. Furthermore, network pharmacology and gene ontology analysis were conducted to determine the multi-mechanistic role of eugenol in treating pain, inflammation and associated malfunctions. The results showed that among the four developed formulations, F3 formulation was found as the optimized formulation with the average drug content 1.584 +/- 0.070 mg/g. Evaluation of post-formulation parameters such as pH, spreadability, viscosity and FT-IR showed the optimistic characteristic of the optimized formulation. Furthermore, in network pharmacology and gene ontology (GO) study, it can be demonstrated that the developed eugenol based formulation play multiple physiological actions such as regulation of angiogenesis, inflammatory response, dopaminergic synapse, response to reactive oxygen species, etc., via regulation of genes such as ALOX5, BDKRB2, CASP3, MAOA, SCN10A, SCN11A, UGT1A7, VR1 etc., It can be demonstrated that the developed formulation provides an effective pharmaceutical formulation with potent analgesic and anti-inflammatory property.