A study on the phytochemical profile, proximate composition, and antimicrobial activity of Andrographis paniculata leaf extract was carried out. The extract (300g) was obtained by extraction in ethanol at 400ml and was evaluated for antimicrobial activity for seven (7) weeks against fifteen (15) microbial species by determining the Minimum Inhibitory Concentration (MIC) based on the mean diameter zone of inhibition around the disc in millimeters. The ethanolic extract was analyzed for quantitative and qualitative composition of phytochemical profiling. The qualitative screening showed the presence of flavonoids, alkaloids, tannins, cardiac glycosides, terpenes, and glycosides while saponins and anthraquinones were not detected. The quantitative composition of the extract was; alkaloids (1.17±0.19), terpenes (11.48±0.36), tannins (4.73±0.13), flavonoids (0.73±0.00), cardiac glycosides (0.50±0.05) and glycosides (89.48±0.73). The proximate composition showed that carbohydrates and proteins were the most abundant followed by crude fiber and moisture content. The antimicrobial activity of the extract was tested against, Pseudomonas sp, Bacillus cereus, Lactobacillus sp, Staphylococcus aureus, Micrococcus sp, Enterobacter sp, Aspergillus niger, Saccharomyces sp, Bacillus subtilis, Streptococcus sp, Citrobacter sp, Rhizopus sp, Mucor sp, Candida sp and Fusarium sp through the measurement of zone of inhibition, the extract exhibited potent antimicrobial activity against both Gram-negative and Gram-positive bacteria under investigation with diameter of inhibition greater than 1 mm. A similar observation was recorded for the fungi species. The study has demonstrated that Andrographis paniculata leaf extract exhibits potent antimicrobial activity against some selected food spoilage organisms and in bread.