The emergence and spread of drug resistance against most antimalarials on the market raises an urgent need for new therapeutics. Benzylmenadiones (bMDs) are redox subversive substrates of flavoenzymes with potent antiparasitic activity against the blood stages of the human pathogen Plasmodium falciparum (Pf). The lead bMD is active against chloroquine and atovaquone-resistant Pf strains and has an IC50 in the nM range. Parasites are exposed to many oxidative stresses during their development, notably upon haemoglobin digestion and key flavoenzymes, such as the glutathione reductase (GR), are essential to maintain their redox homeostasis. The lead bMD is a subversive substrate of recombinant PfGR that was recently validated as an excellent drug target. Indeed, it is not only essential during parasite multiplication in human erythrocytes, but also in mosquitoes, suggesting that subversive redox substrates for GR could be excellent drugs that both treat people and block parasite transmission. Here we report a robust in vivo assay to assess the efficiency of antimalarial compounds as transmission blocking drugs. We show that bMDs are effective against multiple parasite developmental stages and reduce both parasitemia in mice and parasite transmission to mosquitoes. We will further discuss the characterization of the mode of action of benzylMD.