Tuberculosis (TB) remains a major public-health problem, and drug resistance sustains the search for new antimycobacterial leads, including those from medicinal plants. The present study evaluated the ethanolic leaf extract of Barleria prionitis Linn. (EEBP; Acanthaceae) by phytochemical, chromatographic, computational and microbiological approaches. Leaves collected in Theni district, Tamil Nadu, were extracted with ethanol in a Soxhlet apparatus. Preliminary screening showed alkaloids, carbohydrates, glycosides, sterols, flavonoids, phenols, terpenoids and tannins. Thin-layer chromatography indicated phenolic, terpenoid and steroidal constituents, and GC-MS analysis resolved 60 peaks. Spectrophotometric estimation gave 22.57 mg ursolic acid equivalents/g (terpenoids), 24.62 mg cholesterol equivalents/g (sterols) and 25.04 mg gallic acid equivalents/g (phenols) of extract. Six GC-MS constituents were docked against the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) using AutoDock. Epilupeol (−9.4 kcal/mol) and γ-sitosterol (−9.3 kcal/mol) gave the strongest predicted binding, followed by 2-methoxy-4-vinylphenol (−7.0), diethyl phthalate (−6.9), 1,2,3-benzenetriol (−6.3) and n-hexadecanoic acid (−6.2). Both top-scoring ligands exceeded Lipinski’s logP limit, so their oral drug-likeness is doubtful. In the microplate Alamar Blue assay against M. tuberculosis H37Rv (ATCC 27294), EEBP showed a minimum inhibitory concentration (MIC) of 25 µg/mL, which is eight-fold higher than that of pyrazinamide (3.125 µg/mL) in the same assay. EEBP therefore shows moderate in-vitro antimycobacterial activity and merits bioassay-guided isolation of its triterpenoid and sterol constituents; the docking predictions are hypotheses that require enzymatic and cellular validation.