Different processing methods significantly affect the content of bioactivities and the anti-oxidant activities in food sources, including black rice, one of the world's major food sources of black rice anthocyanin extract (BRAE). In this study, the effect of drum-drying and extrusion processes on lipopolysaccharide (LPS)-induced inflammatory responses by bioactive compounds and antioxidants from black rice extract was determined. This study identified the total phenolic, flavonoid, and anthocyanin contents and antioxidant activities in vitro. The phytochemical constituent analysis of three anthocyanin-enriched extracts from raw (BRAE), drum-dried (D-BRAE), and extruded black rice (E-BRAE) using UPLC-LTQ-Orbitrap-MS/MS tentatively identified nine compounds. Cyanidin-3-glucoside was the major anthocyanin in black rice extracts. In contrast, significant reduced levels of cyanidin-3-glucoside and peonidin-3-glucoside were found in D-BRAE and E-BRAE, and the content of protocatechuic acid was increased obviously in E-BRAE. The anti-inflammatory effects of differently processed rice extracts in LPS-stimulated RAW264.7 cells demonstrated that BRAE, D-BRAE, and E-BRAE (400 μg/mL) significantly inhibited NO and PGE2 secretion (p < 0.001) by down-regulating iNOS and COX-2 mRNA and protein expression levels. mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) were also decreased by BRAE, D-BRAE, and E-BRAE. Therefore, the anti-inflammatory activities of BRAE were not affected by drum-dried or extrusion process. Activation of MAPK and NF-κB pathways were inhibited by BRAE that influenced the regulation of the phosphorylation of JNK, ERK, p65, and IκBα. These pathways were not affected by the drum-dried process but were significantly enhanced by the extrusion process. This study will provide scientific and meaningful basics for the application of BRAE using different processing methods in anti-oxidant and anti-inflammation.