Abstract: Extremophile strain Monascus pilosus YX-1125 was isolated from the baijiu-making environment. It was found that this strain could use sorghum as substrate and could tolerate multiple extreme environmental stress. Based on this, Monascus and Sorghum Fermentation Filtrate (MSFF) derived from this strain was developed, and its composition, safety, and bioactivity were studied. Research findings revealed that MSFF was abundant in various bioactive substances, including short-chain fatty acids such as propionic acid, butyric acid, and acetic acid, phenolic compounds (greater than 7.0 mg/mL) and 17 amino acids (greater than 7.5 mg/mL), and had strong antioxidant potentials (80% concentration of MSFF with DPPH scavenging 67.3%, copper chelation 59.71%, iron chelation 42.62%, hydroxyl scavenging 83.31%, superoxide scavenging 55.8%, and ferric ion reducing antioxidant power 1.24 mmoL eq FeSO₄/mL). The results of in vitro experiments revealed that 1% (v/v) MSFF could inhibit inflammation and reduce its damage by reducing 81.4% cell apoptosis, removing 35.8% intracellular reactive oxygen species, inhibiting the release of proinflammatory cytokines (interleukins-6 and -8) up to 83.2% and down-regulating the expression of matrix metalloproteinases (MMP-1 and MMP-9) up to 42.5%. The safety test confirmed that MSFF had high cytocompatibility. In conclusion, MSFF was a safe and highly effective antioxidant and anti-inflammatory ingredient, which had great potential applications in the fields of health food and skincare.