In an attempt to treat infection of mice skin, and investigate the antimicrobial effect of bacterial system (G-system) using essential oil and methanol extract of Tagetes patula flowers (Qadifah), several experiments were carried out. These extracts were investigated for the presence of some active secondary metabolites and their antimicrobial activity. Tagetes methanol flowers extract contained phenols, flavonoide, alkaloids, saponins, and terpenes. This extract showed an inhibitory effect better than essential oil (undiluted) against Staphylococcus aureus, Pseudomonas aeruginosa, Klebseilla pneumoniae, and Candida albicans. Escherichia coli was resistant to both essential oil and methanol extracts. Essential oil (undiluted) and methanol extract (50mg/ml) showed better inhibitory activity against S. aureus, thus those extracts were applied on laboratory mice skin. Essential oil and methanol extract had antibacterial, anti-inflammatory and healing effect as compared with the commercial skin ointment (Samacycline) on mice skin infected with S. aureus. Methanol extract was rich in flavonoides, and showed no cytotoxic effect on the G-systems [Bacillus spp. (G3), Arethrobacter spp. (G12), and Brevibacterium spp. (G27)]. The interaction treatments (per, simu, and post) of the drug (Methotrexate) at the concentration 50μg/ml and methanol extract at concentration 50mg/ml were employed to reduce the activity of drug on the bacterial system.