BVDV has gained prominence as a leading pathogen among cattle due to considerable economic losses arising from its causation of bovine viral diarrhea and mucosal disease. Despite the exhaustive research carried out, mechanisms for persistent infection and mucosal disease remain poorly understood, and effective anti-viral treatments lack application. Dihydroartemisinin (DHA) is a derivative of artemisinin that has some potential antiviral properties, including inhibitory activity against SARS-CoV-2, aside from being an endoplasmic reticulum stress modulator. The following study explored the antiviral properties of DHA against BVDV replication and its possible mechanisms. In in vitro cell culture models, DHA was tested at a concentration of 40 μM without showing any effect on cell viability. The modulatory effects of DHA on ERS and its involvement in viral replication were also investigated. It was observed that DHA strongly suppressed BVDV replication and indicated the possibility of the antiviral potency of DHA being mediated by mitigating ERS and the unfolded protein response. These findings supported the possible use of DHA as a new therapeutic agent in controlling BVDV infections. Further studies may elucidate, in detail, the molecular pathways that are involved and also assess the in vivo efficacy of DHA and its wider applicability against other viral infections.