Coronavirus disease 19 (COVID-19) has posed serious threats to the general population. To relieve the crisis, a comparison of drug effects against COVID-19 is instructive. Between January 27, 2020 and March 21, 2020, a total of 333 patients treated with arbidol, corticosteroids, hydroxychloroquine, lopinavir/ritonavir, or oseltamivir monotherapy, having definite outcomes and serological antibody detection results, were retrospectively analyzed. The hydroxychloroquine group had a significantly reduced duration of hospital stay than the arbidol and corticosteroids groups. The oseltamivir group had a significantly shorter length of hospital stay than the arbidol, corticosteroids, and lopinavir/ritonavir groups. The hydroxychloroquine group had a significantly higher IgM titer than the other four groups and exhibited significantly higher IgG levels than the arbidol, lopinavir/ritonavir, and oseltamivir groups. Our findings indicated that hydroxychloroquine might have the potential for efficient COVID-19 management, while oseltamivir should be prudently considered in combination therapy.