Malaria is a life-threatening disease caused by parasites of the genus Plasmodium and is transmitted to humans by the bite of female mosquitoes of the genus Anopheles. WHO has reported 219 million cases of malaria and 435,000 deaths were estimated in 2017. The anti-malarial treatment more frequently used is based on Chloroquine, which has been used for several decades. This prolonged application has caused the parasite to develop resistance to the use of the mentioned drug, so it becomes necessary to search for new treatments. In addition, some tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (THTT) derivatives have been previously studied as possible trypanosomicides, obtaining satisfactory results in the treatment to Trypanosoma cruzi; Trichomonas vaginalis and T. b. rhodesiense, although no studies against malaria have been reported. In the present work, six bis-THTT derivatives were evaluated as potential anti-malarial drugs (JH1, JH2, JH3, JH4, JH5, and JH6) with BALB/c mice, which were inoculated with Plasmodium berghei ANKA strain and Plasmodium yoelii 17XL strain. The percentages of parasitemia were determined for each tested compound, which was assessed daily on smears from tail blood, stained with Giemsa’s reagent and observed under light microscopy as evidence of cure. Our results showed that JH2 and JH4 presented effective parasitemia control similar to chloroquine in P. berghei. Besides, JH5 and JH6 exhibited better results than Chloroquine with P. yoelii infection. In summary, four of the six bis-THTT derivatives tested, could be considerate as potential new drugs to infection malaria rodent control. Immune response essays should be realized in order to confirm our preliminary results.