Background: Pleurotus ostreatus (Oyster) is a worldwide used mushroom, known to have a wide range of nutrients. Effects of the ethanolic and aqueous extracts of Oyster and its isolated proteins on the production profiles and bio health markers in broiler birds were evaluated in the present research. Methods: Four hundred and twenty, day-old Ross-308 broiler birds were distributed into seven groups with sixty number of birds in each group (N=60). Each group was divided into three subgroups with twenty number of birds in each subgroup (N=20). The first group was selected as control (CONT) with no treatment and other six groups were supplemented orally with the mushroom protein at a dose of 200 (Pr200) and 400mg/Kg BW (Pr400), an aqueous extract of mushroom at a dose of 200 (Aq200) and 400mg/Kg BW (Aq400) and ethanolic extract of mushroom at a dose of 200 (Eth200) and 400mg/Kg BW (Eth400) respectively. On day 28th of the experiment, 1st sub-group of each group was evaluated for cell-mediated immunity by assessing the lymphoproliferative reaction to Phytohemagglutinin-P (PHA-P; Toe web assay) and the humoral immune reaction was evaluated in the 2nd subgroup of each group by antibody reaction to sheep red blood cells (sRBCs; Hemagglutination assay). On day 42, serum was separated by slaughtering (decapitation) all the birds and evaluated for the oxidative stress, lipid profile, blood glucose level, and immune parameters. One-way analysis of variance (ANOVA), Tuckey range tests, and geometric mean titer (GMT) was used to statistically analyze the results. Results: The Eth400 birds showed significantly (P<0.05) higher cell-mediated immune response (1.1±0.04 mm) and humoral immune response (49.31±0.03 mm) in comparison with the control group. Birds supplemented with mushroom extracts and protein revealed significantly greater growth performance, maximum in Eth400, in terms of feed conversion ratios (FCR; 1.44±0.002) when compared with the control group (1.7±0.01). Conclusion: Different parameters to evaluate oxidative stress showed that the mushroom extracts and its protein reduced the oxidative stress in the treated groups being maximum in Eth400. Conclusively, the oyster mushroom has health promoting effects in term of production profile, as immunomodulator and antioxidant in broiler poultry.