In this chapter, a literature survey was performed to identify the best African plants and their derived phytochemicals with anti-Helicobacter pylori activity. Based on the established cut-off points for the classification of antibacterial activity of natural products, the most active African botanicals against Helicobacter pylori were identified as Lippia javanica, Eucalyptus grandis, Eryngium foetidum, Scleria striatinux, Lycopodium cernua, Ageratum conyzoides, Terminalia spinose, Eucalyptus camaldulensis, Eucalytus torelliana, Erythrina speciosa, Bidens pilosa, Galinsoga ciliata, Bryophyllum pinnatum, Spathodea campanulata, Peltophorum africanum, Eucalyptus globulus, and Harrisonia abyssinica. The phytochemicals exhibiting outstanding and excellent activities were identified as terpinen-4-ol (1), vokensiflavone (2), gingerol (3), fraxetin (4), 2-methoxy-1,4-naphthoquinone (5), 2-methoxy-6-acetyl-7-methyljuglone (6), 2-ethoxy-6-acetyl-7-methyljuglone (7), 2-methoxy-7-acetonyljuglone (8), 3-acetyl-7-methoxy-2-methyljuglone (9), juglone (10), polydatin (11), fuscaxanthones A (13), G (17) and I (12), cowanin (14), cowaxanthone (15), cowanol (16), fukugiside (18), berberine (19), pyrrolidine heterocyclic (20), 1-methyl-2- [(Z)-8-tridecenyl]-4-(1H)-quinolone (21), 1-methyl-2-[(Z)-7- tridecenyl]-4-(1H)-quinolone (22), ent-kaurenoic acid, emodin, α and β-mangostins, isojacareubin aned 1,3,5,6-tetrahydroxyxanthone. The identified plants and phytochemicals are potential sources of drugs and should be further explored to develop herbal medicine and pharmaceuticals to combat Helicobacter pylori infections involving both sensitive and resistant phenotypes.