Piper acre Blume (Piperaceae) is an Indonesia native plant that is used as a traditional medicine and commonly known as ‘Sirih Hitam’ or ‘Sirih Hutan’. The scientific data from the plant is still very limited. The aims of the present study was to know a pharmacognostic, and cytotoxicity of P. acre Blume leaf. The macroscopic characters showed that the leaves have a characteristic odor, heart-shaped, margin was finely flat, venation was curved, the upper surface was dark green and slippery while the lower surface was pale green and soft. The microscopic characters revealed upper and lower epidermis cells, glandular trichomes, concentric vascular bundle, paracytic stomata. The fluorescence characteristics showed a variety of chemical constituents present in the plant materials. The preliminary phytochemical investigation of various extracts showed the presence of alkaloid, flavonoid, saponin, terpenoid, tannin, carotenoid, and steroid. The physicochemical properties (yield, color, consistency) of the n-hexane, ethyl acetate, and ethanol extract were 31.57% w/w (green concentrated solid), 13,59% w/w (green concentrated solid), and 16.35% w/w (brownish green liquid). Based on the cytotoxicity using brine shrimp lethality assay of the n-hexane extract (2.46 μg/ml), ethyl acetate extract (0.925 μg/ml), and ethanol extract (5.741 μg/ml) showed that the extract had the cytotoxic activity.