The liver stage of hypnozoite-forming species (P. vivax and P. ovale) is considered an important chemotherapeutic target due to the role of hypnozoites in extending their parasitological and epidemiological persistence. Chemotherapies for eliminating Plasmodium hypnozoites are limited to primaquine and tafenoquine. However, potentially dangerous or fatal haemolysis restricts their use making it urgent to find novel hypnozoitocidal compounds. We undertook a comparative evaluation of the anti-parasitic activity of infusions prepared from an Artemisia species (A. annua) with high artemisinin content and another A. afra with low artemisinin content, in in vitro cultures of the hepatic stages of P. vivax and P. cynomolgi. Interestingly, at doses that are not toxic to the primary hepatocytes, both infusions were equally effective in eliminating parasites especially when cultures were treated early after sporozoite inoculation. Confocal microscopic examination following exposure to either infusions revealed disruption of the parasites’ apicoplast (including in hypnozoite) which might have been mediated by a non-artemisinin component and that might have led to parasite killing. Taken together, our results open up a potential avenue to identify a novel class of compounds present in Artemisia that might be active against hypnozoites.