Multidrug-resistant (MDR) bacteria are a major threat throughout the world. Predatory bacteria, often referred to as Bdellovibrio-and-Like-Organisms (BALOs), are a promising alternative to antibiotics for treating MDR strains as BALOs are capable of predating on more than 140 different human pathogens. However, how the host responds to these bacteria is still an area of investigation. Towards this end, we investigated the responses of four human epithelial cells (Nuli-1 airway, Caco2, HT29, and T84 colorectal cells) and a murine macrophage (Raw 264.7) when exposed for up to 24 hr to three different BALOs (multiplicity of infection (MOI) = 1230) or E. coli MG1655 (MOI = 111). To evaluate their responses, we considered the viability, cytokine production, and actin filament structure. Each BALO strain caused, at most, only a mild cytokine response, with no significant change in either the cell viability or morphology, while E. coli elicited strong TNFa and IL-8 production levels in several of the cell lines as well as led to significant losses in their viability. Subsequently, we investigated the responses with an invasive bacterial strain and B. bacteriovorus 109J together and found that predation reduced the adverse impacts, i.e., viability and cytokine response. These studies show that not only are predatory bacteria safe, i.e., not immunogenic or harmful towards human cells, but their activities are effective at reducing the cellular inflammatory response towards potential human pathogens.