Background: The use of combinational approach in chemotherapeutic management has proven more effective against infectious disease and lower resistance development but the untoward effect of this is yet to be explored for alternative medicine. Aims: This study aimed to study the effect of a combinational approach of herbal drugs on Escherichia coli response. Methods: E. coli was treated in different concentrations of combined herbal drugs (Beta herbal drugs and Deep root herbal mixture – BD) and (Beta herbal drug and Goko cleanser – BG). The different concentrations of the mixtures employed were: 33.3%, 11.1%, 3.7%, 1.2% and 0.4%. The bacteria concentration of 103 CFU/ml was treated in the different concentrations of the herbal drugs. The growth response of the cultures were analyzed at 24 and 48 hrs. The antibiotic sensitivity of the bacteria exposed to the herbal drugs were measured against perfloxacin (PEF), ciprofloxacin (CIP), streptomycin (S), and septrin (SEP). Results: The growth response curve showed growth of E. coli peaked in the lower concentrations but levelled down in the higher concentrations. 24 hr growth conditions showed much higher growth level than 48 hr. Higher concentrations of BG drug combination showed higher zones of clearance and only one concentration showed resistance: 0.4% (CIP). There was no unique pattern seen in the sensitivity of E. coli treated with BD however, there was five (5) cases of complete resistance: 0.4% (PEF), 1.2% (PEF) and 11.1% (CIP and SEP). Conclusion: In vitro, the combined herbal drugs do not completely eliminate E. coli. However, some concentrations of the combinations demonstrated complete resistance to the antibiotics which shows that these locally made antimicrobial could confer antibiotic resistance to E. coli.