Background The resistance to antibiotics shown by some dermatological pathogenic microorganisms has increased the interest of pharmaceutical and cosmetic industries in developing natural products that possess different biological activities, including antimicrobial effects. Methods In the present investigation, the antibacterial activity of ethanolic extracts of Dodonaea viscosa aerial part and Mammea americana leaves and seed was evaluated against resistant strains of Staphylococcus isolated from skin lesions and against S. aureus ATCC 25923 (reference strain). Column chromatography (CC) and preparative thin-layer chromatography (PTLC) were used to obtain separate fractions of the seed extract of M. americana. We also determined the antimicrobial resistance of the strains against antibiotics using the agar disc diffusion assay. In addition, phytochemical screening was performed by colorimetric standard techniques. Results M. americana seed extract showed the highest antibacterial activity with MBC from 2.3 μg/mL to 19.5 μg/mL without differences with gentamicin (p = 0.998). The isolated strain S. epidermidis I showed the highest antimicrobial resistance against the tested antibiotics. PTLC-fractions of M. americana seed extract showed MBC from 3.2 μg/mL to 40.7 μg/mL against S. epidermidis I and S. aureus 25923 (reference), respectively, which suggests a synergistic effect of the secondary metabolites present in the crude ethanolic extract compared to its active PTLC-fractions, where only coumarins and compounds with lactone groups were detected in the phytochemical screening. Conclusion M. americana seed extract has promising effects that should be considered in further studies as an alternative or adjuvant in treating skin infections caused by staphylococci.