Background: Piper guineense commonly known as “West African black pepper”, “Ashanti pepper” or “iyere” in Yoruba land (Southwestern Nigeria). Objective: Powdered seed was screened for its phytochemical and antimicrobial properties because for its ethno medicinal claims as being used in the treatment of various microbial and parasitic infections. Methodology: Sun dried seeds of Piper guineense were screened for its phytochemical constituents and antimicrobial activity using ethanol, n-hexane and water extracts. The antimicrobial activities of the extracts were determined based on the presence and absence of zones of inhibition. Findings: The seeds extracts of P. guineense contain secondary metabolites such as carotenoids, alkaloids, tannins, saponins anthraquinones, steroids, phenols, flavonoids and terpenes. The aqueous extracts exhibited highest zones of inhibition that ranged from 3-29 mm, followed by ethanol extracts inhibition with zones from 4-22 mm and least with n-hexane inhibition which ranged from 7-14 mm even with concentrations of 400 and 500 mg only. Conclusion: The results of this research suggest that P. guineense is a promising therapeutic agent that could have potential for the treatment of various pathogenic diseases based on the valuable phytochemicals known for microbial inhibition.