The emergence of clinically drug-resistant malaria parasites requires the urgent development of new drugs. Mosquitoes are vectors of multiple pathogens and have developed resistance mechanisms against them, which often involve antimicrobial peptides (AMPs). An-cecB is an AMP of the malaria-transmitting mosquito genus
Anopheles
, and we herein report its antimalarial activity against
Plasmodium falciparum
3D7, the artemisinin-resistant strain 803, and the chloroquine-resistant strain Dd2
in vitro
. We also demonstrate its anti-parasite activity
in vivo
, using the rodent malaria parasite
Plasmodium berghei
(ANKA). We show that An-cecB displays potent antimalarial activity and that its mechanism of action may occur through direct killing of the parasite or through interaction with infected red blood cell membranes. Unfortunately, An-cecB was found to be cytotoxic to mammalian cells and had poor antimalarial activity
in vivo
. However, its truncated peptide An-cecB-1 retained most of its antimalarial activity and avoided its cytotoxicity
in vitro
. An-cecB-1 also showed better antimalarial activity
in vivo
. Mosquito-derived AMPs may provide new ideas for the development of antimalarial drugs against drug-resistant parasites, and An-cecB has potential use as a template for antimalarial peptides.