Simple Summary: Mushroom waste compost is the main byproduct when cultivating mushrooms. Due to its high mycelium content, mushroom waste compost may improve animal health by increasing antioxidant capacity. Furthermore, increasing evidence suggests that supplementing animal diets with fiber could improve body composition and health. The results showed that supplementation with mushroom waste compost accelerates adipolysis and enhances the antioxidant capacity of broilers. Among all treatment groups, broilers given dietary supplementation with 0.5% mushroom waste compost showed improved feed conversion rate and the highest adipose metabolism.Abstract: Pennisetum purpureum Schum No. 2 waste mushroom compost (PWMC) is the main byproduct when cultivating Pleurotus eryngii. Due to the high mycelium levels in PWMC, it may have potential as a feed supplement for broilers. This study investigated the effects of PWMC supplementation on antioxidant capacity and adipose metabolism in broilers. In the study, 240 broilers were randomly allocated to one of four treatment groups: basal diet (control), 0.5%, 1%, or 2% PWMC supplementation. Each treatment group had 60 broilers, divided into three replicates. The results showed that supplementation with 0.5% PWMC decreased the feed conversion rate (FCR) from 1.36 to 1.28, compared to the control. Supplementation with 0.5% or 2% PWMC decreased glucose and triglyceride levels, compared to the control (p < 0.0001), the concentrations of adiponectin and oxytocin increased from 5948 to 5709, 11820, and 7938 ng/ mL; and 259 to 447, 873, and 963 pg/ mL, respectively. Toll-like receptor 4 was slightly increased in the 0.5% and 1% PWMC groups. Both interferon-γ (IFN-γ) and interleukin-1ß (IL-1ß) were significantly decreased, by about three to five times for IFN-γ (p < 0.0001) and 1.1 to 1.6 times for IL-1ß (p = 0.0002). All antioxidant-related mRNA, including nuclear factor erythroid 2-related factor 2 (Nrf-2) and superoxidase dismutase-1 (SOD-1), increased significantly following PWMC supplementation. Both claudin-1 and zonula occludens 1 increased, especially in the 2% PWMC group. Excitatory amino acid transporter 3 (EAAT3) significantly increased by about 5, 12, and 11 times in the 0.5%, 1%, and 2% PWMC groups. All adipolysis-related mRNA were induced in the PWMC treatment groups, further enhancing adipolysis. Overall, 0.5% PWMC supplementation was recommended due to its improving FCR, similar antioxidant capacity, and upregulated adipolysis.