Background: The purpose of this study was to determine the phytochemical composition and antimicrobial potential of crude n-hexane, ethyl-acetate, methanol and aqueous extracts of Calotropis procera leaves against food spoilage microorganisms. Methods: Standard protocols were employed for the analysis of qualitative phytochemical compositions of the extracts, and antimicrobial activities against Staphylococcus aureus, Bacillus cereus, Pseudomonas aerugenosa and Aspergillus niger. Results: Phytochemical analysis revealed the presence of tannin, saponin, alkaloids, flavonoids, reducing sugar and phenolics. Terpenoids were absent in ethyl acetate and n-hexane extracts while cardiac glycoside was absent in all extracts. All extracts produced antimicrobial activity at a varying zone of inhibition. The widest inhibition zone was produced by methanol extract (21.35±0.43 mm) on staphylococcus aureus while the lowest inhibition zone (12.05±0.45 mm) was observed in the n-hexane fraction. Similarly, the widest inhibition zone (17.24±0.95 mm) was produced by methanol on A. niger while the lowest inhibition zone (5.45±0.42 mm) was produced on n-hexane on A. niger. However, the ethyl acetate extract showed no visible inhibitory zone on all the tested microorganisms. The minimum inhibitory concentration ranged from 32 mg/ml (S. aureus and B. cereus) for ethanol extracts to 128 mg/ml (B. cereus, P. aerugenosa and A. niger) for n-hexane extract. Conclusion: The result shows that the plant is a good source of bioactive compounds that can be used as a natural alternative to a chemical agent in preserving and controlling food poisoning organisms.