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Nicotiana glauca belonging to the family Solanaceae is an exotic perinnial bushy species that recently has invaded the mountainous areas of Al-Baha region at the south-west of Saudi Arabia, causing degredation to soil and vegetation composition of those mountains. Accordingly, this plant must be either removed or exploited as a source of useful products such as medicines as it has been proven to contain many effective compounds with therapeutic properties. Thus, the current study aimd to screening N. glauca preliminary phytoconsitiuents and its anticmicrobial activity. Results showed that varying amounts of alkaloids, steroid, tannins, flavonoid, were present in the extracts of N. glauca leaves, stems and flowers. Saponins were present only in the flowers extract. However, all previuos bioactive compounds were absent in the roots except alkaloids, therefore, roots posses lesser amount of the phytoconstituents compared to the other parts of the plants. Leaves extracts inhibited the growth of E. coli (16.3 ± 0.71 mm) and also inhibited the growth of S. aureus (11.0 ± 0.23 mm), while, the flower extracts also inhibited the growth of E. coli (6.7 ± 0.65 mm), and also inhibited the growth of S. aureus (15.8 ± 0.52 mm). This result coincide with the previous results of the screening of N, glauca phytochemicals where the highest amounts found in leaves and flowers extracts. The inhibition zone of the antibiotic gentamycin (reference control) were 32 mm in S. aureus and 38 mm in E. coli. The inhibition zone of gentamycin (reference control) were 32 mm in S. aureus and 38 mm in E. coli. The minimum inhibitory concentration (MIC) of ethyl acetate was ranged (1.5–2 mg/ml). The lower MIC is an indication of high effectiveness of extract. Therefore, such bioactive property would support the idea that removing N. glauca from the mountainous areas of Al-Baha, Saudi Arabia, is not the only solution, but the plant can be exploited as a beneficial source of medicinal and economic purposes such as; antibacterial, antifungal and insecticidal, however, further comprehensive exploration is recommended to confirm such propreties.