Purpose: Extraction of bioactive agents from plant source to combat fungal and bacterial infections. Results: The current study encompasses in vitro antimicrobial activities of methanol, hexane, chloroform, butanol, aqueous, ethanol, ethyl acetate and dimethylsulfoxide extracts of Datura metel, Rosa indica and Citrus sinesis. Phytochemical analysis of the plant extract exhibited the presence of tannins, alkaloids, terpenoids, flavonoids and saponins. These extracts were evaluated for antimicrobial activity using agar disc diffusion method against Escherichia coli, Bacillus spp., Staphylococcus spp., Micrococcus spp., Candida albicans, Aspergillus niger and Aspergillus flavus. The methanol and ethanol extracts of D. metel, R. indica and ethyl acetate extract of C. sinesis were found to be highly potent against the bacterial strains. The chloroform, ethanol and dimethylsulfoxide extracts of C. sinesis and ethanol and chloroform extracts of D. metel, R. indica exhibited the most effective antifungal activity. The minimum inhibitory concentration (MIC) of plant extracts was determined using microdilution method. The MIC was found to be 0.45 to 1.25 mg/mL against bacterial strains and 0.4 to 2.5 mg/mL against fungal strains. It was also observed that these extracts drastically reduce the melanin content of the A. niger which plays a key role in its pathogenicity. The conidial cell wall and colony analysis of A. niger exhibited remarkable reduction in conidia and melanin deposition as seen microscopically and ergosterol content as estimated spectroscopically. Conclusions: Melanin content in the cell wall is a key determinant of fungal pathogenicity making it an attractive target for antifungal drug discovery. Our results are the first report of melanin inhibitory activity of these extracts.