This review examines the synergistic anthelmintic potential of Zingiber officinale (ginger) and Acorus calamus (sweet flag). It summarizes the current literature on their combined use against parasitic worms, focusing on in vitro and in vivo studies. The potential mechanisms underlying their synergistic effects, such as enhanced inhibition of parasite neuromuscular function, disruption of tegument integrity, and modulation of host immune response, are discussed. The review also addresses the safety considerations of using these two plants in combination, with particular emphasis on the use of low β-asarone A. calamus chemotypes. Despite the limited research on their combined anthelmintic activity, this review highlights the promising potential of this plant combination for developing novel anti-parasitic therapies and emphasizes the need for further research to establish its efficacy, safety, and optimal usage.