Membrane-disruptive peptides/peptidomimetics(MDPs)are antimicrobials or anticarcino-gens that present a general killing mechanism through the physical disruption of cell membranes,in contrast to conventional chemotherapeutic drugs,which act on precise targets such as DNA or specific enzymes.Owing to their rapid action,broad-spectrum activity,and mechanisms of action that potentially hinder the development of resistance,MDPs have been increasingly considered as future therapeutics in the drug-resistant era.Recently,growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents.In this review,we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs,and sum-marize the current development and mechanisms of MDPs alone or in combination with other agents.Notably,this review highlights recent advances in the design of various MDP-based drug delivery sys-tems that can improve the therapeutic effect of MDPs,minimize side effects,and promote the co-delivery of multiple chemotherapeutics,for more efficient antimicrobial and anticancer therapy.