The death of many people in tropical countries can be attributed to microbial infection, probably, because synthetic antibiotics are failing in the treatment of these 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 contents of aqueous and ethanol extracts of the root of Cryptolepis sanguinolenta (Lindl.) and the crude sap of Pycnanthus angolensis (Welw) using selected standard bacteria strains (S. aureus (ATCC 25923), S. saprophyticus (ATCC 15305), E. coli (ATCC 25922), S. typhi (ATCC 19430), P. aeruginosa (ATCC 27853), and P. mirabilis (ATCC 49565). 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 also screened for specific phytochemicals and using the Folin Ciocalteu reagent test, their total phenolic contents were determined. The phytochemical screening revealed the presence of alkaloids, cardiac glycosides, and saponins in both Cryptolepis sanguinolenta and Pycnanthus angolensis. For the antimicrobial activities, all the test bacteria were susceptible to the crude sap of Pycnanthus angolensis except P. mirabilis. In the case of the Cryptolepis sanguinolenta, only S. aureus was susceptible to both aqueous and ethanol extracts. The total phenolic content, expressed in g/100g GAE, recorded values of 55.427 ± 4.248 for the crude sap of Pycnanthus angolensis, and 11.642 ± 4.248 and 26.888 ± 4.248 for the aqueous and ethanol extracts of Cryptolepis sanguinolenta, respectively. It was concluded that Cryptolepis sanguinolenta and Pycnanthus angolensis are excellent candidates for further development of antimicrobial agents in the fight against microbial infections given the pressing need for novel efficacious agents.