Pathogenic biofilms are a global health care concern, as they can cause extensive
antibiotic resistance, morbidity, mortality, and thereby substantial economic loss.
Scientific efforts have been made over the past few decades, but so far there is no
effective treatment targeting the bacteria in biofilms. Antimicrobial peptidomimetics
have been proposed as promising potential anti-biofilm agents. Indeed, these structurally
enhanced molecules can mimic the action of peptides but are not susceptible to proteolysis
or immunogenicity, the characteristic limitations of natural peptides. Here, we provide
insights into antibiofilm peptidomimetic strategies and molecular targets, and discuss
the design of two major peptidomimetics classes: AApeptides (N-acylated-N-aminoethyl-substituted
peptides) and peptoids (N-substituted glycine units). In particular, we present details
of their structural diversity and discuss the possible improvements that can be implemented
in order to develop antibiofilm drug alternatives.