Malaria, an endemic mosquito-borne parasitic disease, is a serious public health threat, particularly in pregnancy. About 25 million pregnant women worldwide each year are infected with malaria, which is endemic in sub-Saharan Africa. Malaria during pregnancy poses significant risks to maternal and fetal health, potentially leading to severe outcomes such as preterm delivery, spontaneous miscarriage, and increased infant mortality. Plasmodium falciparum, the causative agent of severe malaria, expresses P-glycoprotein homologue 1 (Pgh1), a transporter that modulates the parasite’s drug susceptibility, thereby reducing the efficacy of aryl amino alcohol-based antimalarials, such as quinine, mefloquine, and halofantrine, which are commonly employed as prophylactic agents during pregnancy. Multidrug resistance arises from amplifications (duplications) within the pgh1 gene, which are caused by the overexpression of the protein, encoded by the pfmdr1 gene. With pfmdr1 expression, P. falciparum is able to efflux out antimalarial drugs, like the weak-base 4-aminoquinolines out of its digestive vacuole, inhibiting its attachment to heme and impeding the body’s natural detoxifying process. Resistance to quinine, mefloquine, and halofantrine has been associated with specific polymorphisms in pfmdr1 (e.g., N86Y, Y184F) and pfCRT (e.g., K76T, A220S). It is essential to understand the mechanisms by which Pgh1 regulation contributes to medication resistance. Developing antimalarial treatments that target Pgh1 may offer avenues for effective antimalarial treatment, better pregnancy, and development of innovative diagnostic methods for the detection of drug-resistant parasites in expectant mothers.