Introduction: In this study, extracts of Acacia nilotica, Elettaria cardamomum, Psidium guajava, and Glycyrrhiza glabra were prepared using supercritical fluid extraction (SFE) at different pressures and 50°C constant temperature. The antimicrobial activities of extracts were evaluated against oral pathogens, namely, Enterococcus faecalis, Streptococcus mutans, Staphylococcus aureus, and Candida albicans. Materials and Methods: The antimicrobial activities of extracts were evaluated against oral pathogens using agar well diffusion method. Phytochemical analysis of A. nilotica twig was done using gas chromatography-mass spectrometry (GCMS). Statistical analyses of data were performed by one-way ANOVA using MS-Excel and principal component analysis was performed using statistical software XLSTAT 2018. Results: All plants extracts exhibited significant activity at P < 0.05 with inhibitory zones ranging from 8 to 42 mm and minimum inhibitory concentration (MIC) values from 0.19 to 3.12 mg/ml. A. nilotica twig extract obtained at 400 bar pressure showed the highest zone of inhibition (42.07 mm) and lowest MIC (190 µg/mL). E. cardamomum and G. glabra extracts showed moderate activity while P. guajava extracts showed least activity against the oral pathogens. GC-MS analysis of A. nilotica twig confirm the presence of functional moieties of stigmasterol, clionasterol, betulinaldehyde, eugenol, α-terpinyl acetate, and 22,23-dihydrobrassicasterol in the extract which could be responsible for its antimicrobial efficacy and may prove beneficial in oral care products. Conclusion: The extraction of antimicrobial agents from plant materials using SFE at low temperatures avoids the thermal degradation and use of toxic solvents. A. nilotica twig at 50°C and 400 bar showed the significant antimicrobial potential, hence it can be processed to obtain effective and cheaper drug due to higher biomass availability. Chemical profiling of SFE extract by GC-MS analysis proved helpful in the identification of compounds. Furthermore, bioactive compounds should be explicated for their exact mechanism of action with the target pathogens.