"Minimalist" antimicrobial peptides are disclosed based on 50 to 80% .alpha.,.alpha.-dialkylated amino acids. The peptides are short, cationic, amphipathic, and possess a high helix propensity. Polar .alpha.,.alpha.-dialkylated amino acids are also disclosed. These peptides are easy and inexpensive to synthesize via solid-phase techniques. The peptides exhibit in vitro anti-bacterial properties at concentrations that are not lethal to normal mammalian cells. The peptides exhibit in vivo bioactivity against intracellular pathogens.