Oyster mushroom stem residue, a by-product with medicinal and nutritive values, might be a prospective feed supplement in poultry nutrition. The study focused on evaluating the impact of oyster mushroom (Pleurotus ostreatus) stem residue (OMSR) powder supplementation on growth performance, carcass traits, meat quality, blood characteristics, and the cecal bacterial count in Arbor Acres broilers raised 35 d. A total of 144 day-old chicks, with an average weight of 40.27± 2.45 g, were divided into 3 groups: control (received a standard basal diet), antibiotic (basal diet + 75 mg/kg chlortetracycline), and OMSR (fed a basal diet with 300 mg/kg OMSR), where each group comprises 8 replications of 6 chicks. Supplementation of 300 mg/kg of OMSR powder in the broiler diet significantly (P < 0.05) enhanced the average daily gain (ADG) and final body weight as opposed to the control and antibiotic treatments, though the average daily feed intake was not influenced by OMSR supplementation during the whole experimental period. However, in comparison to the control and antibiotic groups, OMSR significantly reduced the postmortem breast meat drip loss percentage (P < 0.05) at 24 hours and on the seventh d. Furthermore, the OMSR group reported significantly elevated levels of Hb and RBC counts (P < 0.05), and decreased levels of serum triglyceride (TG) and total cholesterol (TC) concentrations (P < 0.05) on d 35 in comparison to broilers in the control and antibiotic groups. Additionally, the OMSR group exhibited an improved Heterophil/Lymphocytes (H/L) ratio (P < 0.05) relative to the broilers of the control and antibiotic groups. In contrast, the inclusion of OMSR in the broiler diet did not significantly (P > 0.05) influence other serum biochemical and hematological values tested. Broilers in OMSR group had reduced number (P < 0.05) of E. coli and Salmonella spp., but higher presence of Lactobacillus spp. (P < 0.05) in contrast to the control broilers. To summarize, the study's findings revealed that 300 mg of OMSR powder supplementation per kg of basal diet could be act as a natural growth promoter, and confer favorable effects on health and meat quality of broilers.