This study explores the formulation and evaluation of an antimicrobial gel derived from Plectranthusamboinicus (Lour) Spreng leaves extract. With a rising global incidence of microbial infections, effective treatments are crucial, especially against pathogens like Staphylococcus aureus and Escherichia coli that cause both local and systemic infections. Plectranthusamboinicus, known for its historical use in traditional medicine for its potential antimicrobial and anti-inflammatory properties. The gel formulation involved incorporating the plant extract into a carboxymethyl cellulose (CMC) base, followed by evaluations include physicochemical parameters such as pH (5.8), appearance (brown), viscosity (7215cps), and spreadability (3.9 gm.cm/sec) were assessed to ensure suitability for topical application. Antimicrobial efficacy was evaluated using Minimum Inhibitory Concentration (MIC) and Zone of Inhibition assays against E. coli and S. aureus, demonstrating inhibition at concentrations above 500 μg/ml. The gel also exhibited significant anti-inflammatory activity compared to diclofenac, a standard anti-inflammatory drug, across various concentrations. Phytochemical analysis via HPLC identified gallic acid as a major component, contributing to the gel's therapeutic potential. Plectranthusamboinicus as a promising source of natural antimicrobial agents, potentially offering safer alternatives to synthetic drugs with reduced side effects.