Novel peptide analogs of a θ-defensin have been developed that provide a biphasic effect in treating infection and/or sepsis. These analogs are active at concentrations below those needed to provide a bactericidal or bacteriostatic effect, and function by initially recruiting effector cells of the immune system to address the infective organism followed by regulation of the immune system to down regulate the inflammatory response characteristic of sepsis and septic shock. These novel θ-defensin analogs are protective at concentrations where naturally occurring θ-defensins have no apparent effect, and include a core set of structural and sequence features not found in native θ-defensin.