Coccoloba peltata Schott (C. peltata) is an evergreen, small tree mainly growing in Brazil. Since there is no relevant report for its biological activities or phytochemical data, this study aimed to assess the volatile components and bioactivity potential of leaves extract and fractions of C. peltata Schott cultivated in Egypt. Gas chromatography mass spectrometry (GC-MS) analysis allowed the tentative identification of thirty secondary metabolites including α-tocospiro A (17.20%), α-tocospiro B (12.02%), squalene (7.78%), 13-epi-manoyl oxide (6.80%), nonacosane (5.12%), pentatriacontane (4.17%) and hexadecanoic acid methyl ester (3.78%) as major compounds. The crude extract was subjected to in vitro bioassays revealing a promising results against the studied cancer cell lines, HepG-2, MCF-7, HCT-116, PC3 and HeLa (IC50 7.56-14.26 µg/mL) in comparison to doxorubicin while the corresponding fractions exihibited lower activity. The antioxidant assay based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ascorbic acid as a reference, indicated the crude extract as the most active (IC50 32.86 µg/mL) followed by chloroform fraction (IC50 46.05 µg/mL), n-hexane fraction (IC50 57.42 µg/mL) and then butanol fraction (IC50 50.06 µg/mL). Finally, the total extract exihibited potent antimicrobial activity against E. coli B. subtilis and C. albicans with activity indices of 46.1, 73.9, 81.5%, respectively, as compared to ciprofloxacin and clotrimazole. Taken together, the crude extract from Coccoloba peltata displayed higher responses to the various assays, it has been suggested as a synergism among the compounds therefore.