Indigenous Saccharomyces (S.) cerevisiae was cultured under submerged fermentation conditions and β-glucans were extracted by enzymatic method. The extracted β-glucans were characterized by FT-IR and their spectra presented peaks at a wavelength of 1021 cm^-1. Safety and mutagenicity testing of β-glucans showed them non-mutagenic and non-toxic up to a concentration of 200 mg/mL. For immunotherapeutic effects against Salmonella (Sal.) typhimurium infection, broiler chicks (n=120) were randomly divided into 4 equal groups viz. A (negative control), B (positive control challenged with Sal. typhimurium; 1.0× 10¹⁰ cfu), C (β-glucans at the dose rate of 50 mg/kg feed + Sal. typhimurium challenge), and D (β-glucans at the dose rate of 100 mg/kg feed + Sal. typhimurium challenge). Results revealed protective effects of β-glucans against Sal. typhimurium infection as depicted by mild clinical signs along with minimal/no gross and histopathological lesions. Immunological responses were also higher (P<0.05) in β-glucans administered birds. β-glucans also modulated intestinal morphology with improved villi-height and crypt-depth ratio. In conclusion, β-glucans isolated from indigenous S. cerevisiae conferred protective effects against salmonellosis and therefore can be used successfully in broilers.