China is a major producer of oats; the annual harvested area of 350,000 ha yields approximately 465,000 tons, giving an average yield of 1.33 tons/ha. The bran is not used for animal feed as it is of poor digestibility and low nutritive content and is considered a waste byproduct. Therefore, it is advantageous to produce a value-added product from the bran. We extracted the native polysaccharide, a linear (1–3)-, (1–4)-linked β-glucan (OBG) from the oat bran and synthesized a sulfated derivative OBGS containing 36.5% sulfate. OBGS had potent activity against a primary isolate of human immunodeficiency virus (HIV-1) in peripheral blood mononuclear cells at a concentration (EC50 = 5.98 ×10−4 µM) approximately 15,000 times below its cytotoxic concentration. OBGS was also active postinfection (EC50 = 5.3 ×10−4 µM) and protected pretreated peripheral mononuclear cells (EC50 = 5.2 ×10−2 µM) washed free of the compounds prior to infection. Thus, OBGS has potential as a vaginal microbicide and is the first such report for oat bran derived sulfated̃ β-glucan.