A polysaccharide (MAR-10) was isolated from the aqueous extract of the plant Hyssop officinalis and examined for its activity against HIV-1 (SF strain) in HUT78 T cell line and primary cultures of peripheral blood mononuclear cells. MAR-10, in a concentration-dependent manner, inhibited HIV-1 replication as demonstrated by the inhibition of HIV-1 p24 antigen and syncytia formation. Furthermore, MAR-10 had no significant direct toxicity or effect on lymphocyte functions or CD4+ and CD8+ T cell counts. In addition, MAR-10 has broad spectrum anti-glycosidase activity. Our study demonstrates that MAR-10 contains strong anti-HIV-1 activity that may be useful in the treatment of patients with HIV-1 infection.