The death of many people in tropical countries can be attributed to microbial infection, probably, because synthetic antibiotics are failing in the treatment of most microbial infections, attributed to the ability of the microorganisms to mutate and adapt to harsh conditions. This study evaluated, in vitro, the antimicrobial activities, antioxidant potentials, and the total phenolic as well as phytochemical contents of aqueous and ethanol extracts of the root ofCryptolepis sanguinolenta(Lindl.) and the crude sap ofPycnanthus angolensis(Welw) using selected standard bacteria strains (Staphylococcus aureus(ATCC 25,923),Staphylococcus saprophyticus(ATCC 15,305),Escherichia coli(ATCC 25,922),Salmonella typhi(ATCC 19,430),Pseudomonas aeruginosa(ATCC 27,853), andProteus mirabilis(ATCC 49,565). The modified agar well diffusion method was used to evaluate the antimicrobial activities of the plant extracts. Chloramphenicol and tetracycline were used as positive controls. The extracts were screened for specific phytochemicals with total phenolic contents were determined using Folin Ciocalteu reagent test. The phytoconstituents observed were alkaloids, cardiac glycosides, and saponins in bothCryptolepis sanguinolentaandPycnanthus angolensis. For the antimicrobial activities, all the test bacteria were susceptible to the crude sap ofPycnanthus angolensisexceptProteus mirabilis. In the case of theCryptolepis sanguinolenta, onlyS. aureuswas susceptible to both aqueous and ethanol extracts. The total phenolic content, expressed in g/100 g GAE, recorded values of 55.427 ± 4.248 for the crude sap ofPycnanthus angolensis, and 11.642 ± 4.248 and 26.888 ± 4.248 for the aqueous and ethanol extracts ofCryptolepis sanguinolenta, respectively. It is concluded thatCryptolepis sanguinolentaandPycnanthus angolensisare excellent candidates for further development of antimicrobial agents in the fight against microbial infections given the pressing need for novel efficacious agents.