In Mexico, the use of plants for the extraction of bioactive molecules has gained importance due to antimicrobial resistance in various pathogenic agents. Euphorbia pulcherrima, a native species commonly used as an ornamental plant, was studied in this work for its pharmacological properties against microbial pathogens responsible for dermal infections (S. aureus ATCC1059, E. coli ATCC25721, C. albicans ATCC60143). Methanolic extracts were obtained from stem, leaf, and flower samples collected in Tlaxcala and Puebla, using solvent extraction and a combination of solvent and sonication. The antagonistic effect against pathogenic bacteria was determined through the Kirby-Bauer disk diffusion method, and the qualitative identification of the extracts was carried out using thin-layer chromatography (TLC). Methanolic extracts obtained via both methods exhibited significant inhibitory effects on pathogenic microorganisms. In the TLC plate run, the presence of no polar molecules, likely associated with aromatic compounds, was observed, which according to the literature, are linked to the antagonistic effects. The use of plants for alternative treatments in microbial infections presents a viable option, providing an opportunity to utilize regional natural resources for different purposes.