The present study was conducted to investigate in vitro antimicrobial activity of various extracts obtained from pseudobulbs of an epiphytic orchid Coelogyne speciosa against Staphylococcus aureus strain (ATCC 25923), a clinically important microorganism responsible for many infections. The pseudobulbs of Coelogyne speciosa plants, cultivated under glasshouse conditions, were sampled at M.M. Gryshko National Botanical Garden (Kyiv, Ukraine). Antibacterial activities of the extract obtained from pseudobulbs of Coelogyne speciosa in various solvent systems were assessed. Consequently, five kinds of solvents were used to extract the active ingredients from the pseudobulbs of Coelogyne speciosa. The testing of antibacterial activity of the plant extracts was carried out in vitro by Kirby-Bauer disc diffusion technique. The results revealed that ethanolic extracts from pseudobulbs of Coelogyne speciosa exhibited strong activity against Staphylococcus aureus (inhibition zone diameter was 19 mm), while methanol, ethyl acetate, hexane, and dichloromethane extracts had no antibacterial activities. Therefore, the research showed that ethanolic extracts obtained from pseudobulbs of Coelogyne speciosa possess antibacterial potency against S. aureus and may be used as natural antiseptics and antimicrobial agents in medicine and veterinary practice. The antimicrobial effect exhibited by Coelogyne speciosa extracts is in agreement with previous data on antimicrobial effects documented for numerous orchid species. Given the medicinal importance of the tested microorganisms, the findings of this research are considered to be very promising in the perspective of new drug development from plant sources. Nevertheless, more research should be carried out to evaluate accurately the roles of particular compounds, isolated from pseudobulb of orchid screened, responsible for the antimicrobial activity.