Argel (Solenostemma argel) and Black seeds (Nigella sativa) are important spices available in Sudan and used in traditional medicine to prove health and to fight microbes. This work aim to determine the chemical composition of Argel (S. argel) and Black seed (N. sativa) and their antibacterial activities against E. coli. Plant samples and E. coli strain were brought from Wad Medani City, Gezira State, Sudan. The plant materials were used to run GC-MS analysis and antibacterial test using the standard methods. The results showed that, The main compounds identified from Argel polar extracted, were 3-pentanol, 2,2,4,4- tetramethyle-(15.61%), (3E.5E.7E)-6-Methyl-8-(2,6,6-trimethyl (13.28%), 4H-Pyran-4-one, 2,3-dihydro-3.5-hydroxy (11.8%), and 2,2-Dimethyl-3-[3-methyl-5-(phenylthio) (9.47%), while those of the Black seeds were hexanedecanoic acid (29.44%), Glycerin (18.45%), Octadecadienoic acid (Z,Z) (17.97%), and (R)-(-)-14-Methyl-8-hexadecyn-1-ol (11.95%). Also the aqueous extract of Argel leaves and Black seeds at concentrations of 5% revealed 6 mm and 0 mm inhibition zones, respectively, but the concentration of 25% produced inhibition zone of 17 and 18 mm, respectively, on E. coli isolate. The effort that seeks for cheap, safe and effective natural agents should be continued.