Resistant strains of bacteria has over the years rendered conventional antibiotics ineffective. Consequently, this has resulted to severe infection, prolonged treatment, high cost of treatment and often times death. This study aimed to identify reliable alternative sources of bioactive agents with activity against resistant Staphylococcus aureus, Escherichia coli and Salmonella typhi. Methanol extracts of Acalypha wilkesiana (MEAW), Senna alata (MESA) and Psidium guajava (MEPG) were tested alone and in combination against three clinical isolates. Ciprofloxacin was used as the positive control drug. A combination of Microscopic, macroscopic and molecular protocols was used to identify the test isolates. The antibiotic profiles of the isolates E. coli (E1), S. aureus (S4) and S. typhi (St2) indicated MultiDrug-Resisitant status (MDR). All the extracts demonstrated antibacterial activity against the resistant isolates with zones of inhibition that ranged between 3.1 – 25 mm and minimum inhibitory concentration of 12.5 – 200 mg/ml. Amongst the extracts tested, MESA was found to be the most active extract while MEPG was the least active extract. The combination of the different methanol extracts demonstrated synergistic effects against the test organisms with a fractional inhibitory concentration that ranged between 0.06 – 0.8 mg/ml. The observed antibacterial activity may be linked to the presence of some bioactive components such as phenolic compounds and flavonoids present in the extracts. The results of this study suggest A. wilkesiana, S. alata and P. guajava may represent reliable sources of important bioactive compounds for new drug development.