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The study was carried out to determine the antimicrobial activities of Spondias mombin Linn leaves extract on microbes obtained from human mouth. Plant samples were obtained from a tree in front of student lecture theater, University of Benin. The fresh leaves of S. mombin were rinsed in running water to remove adhering dust particles and later extracted with hot aqueous solution. Following standard procedure the medium prepared was used to culture bacteria on nutrient agar and fungi on malt extract agar. Agar well diffusion method was also used to determine the antimicrobial activities of the plant extract against the oral microbes. The results shows that the highest bacteria count was obtained at 50g/L of plant extract (25.3 x103 cfu/ml), while the lowest count was obtained at 150 g/L (8.3 x103 cfu/ml). Also the highest fungi count was obtained at 50g/L (15.7 x103 cfu/ml), while the lowest count was obtained at 150 g/L (5.3 x103 cfu/ml). Staphylococcus aureus and Pseudomonas aeroginosa isolate had a zone of inhibition of 10 mm and 9 mm at 50g/L, followed by 100g/L (13 mm and 11mm) and 150g/L (15 mm and 13 mm). Aspergillus sp and Saccharomyces sp. isolate had a zone of inhibition of 9 mm and 9 mm at 50g/L, followed by 100g/L (11 mm and 10 mm) and 150g/L (13 mm and 12 mm) respectively. Also media prepared with Spondias mombin extractshowed no fungi growth compared with media prepared without the plant extract. The study suggests that S. mombin fresh leaves extracts can be used as natural alternative to treat infectious diseases caused by the test organisms.