Background: Oroxylum indicum (L.) Kurz is a plant that has been extensively used as the traditional medicine in several Asian countries. However, the role of Oroxylum indicum seeds (OISs) in the antioxidant and anti-inflammatory functions of activated microglia have not yet been identified. Objectives: The present study aimed to investigate the anti-inflammatory and antioxidant role of OIS extract in a neuroinflammatory model of lipopolysaccharide (LPS)-stimulated microglia cells. Materials and Methods: BV2 microglial cells were treated with OIS extract in the presence or absence of LPS for 24 h. Subsequently, the levels of interleukin (IL)-6, nitric oxide (NO), and reactive oxygen species (ROS) were detected through enzyme-linked immunosorbent assay, Griess reagent, and the 2',7'-dichlorofluorescein diacetate fluorescent probe, respectively. In vitro antioxidant capacity was assessed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The total flavonoid and phenolic contents were also investigated. Results: OIS extract increased the levels of antioxidants detected by the DPPH and ABTS assays. The total flavonoid and phenolic content of OIS extract was 325.64 ± 4.95 and 50.47 ± 1.53 mg/g of dried extract, respectively. In addition, the levels of IL-6, NO, and ROS significantly decreased in LPS-induced BV2 microglia cells following treatment with OIS compared with the control. Conclusion: Taken together, the results of the present study demonstrated the antioxidant and anti-inflammatory properties of OIS in activated-BV2 cells. Thus, OIS extract may be used as a potential source of nutraceuticals for the development of health food supplements or as a novel anti-inflammatory herbal medicine.