Phytochemical analysis of a methanol-dichloromethane (1:1) extract of the aerial parts of <i>Tephrosialinearis</i> led to the isolation of 18 compounds. Seven of these, namely, lineaflavones A-D (<b>1</b>-<b>4</b>), 6-methoxygeraldone (<b>5</b>), 8″-acetylobovatin (<b>6</b>), and 5-hydroxy-7-methoxysaniculamin A (<b>7</b>) are new compounds. The compounds were characterized based on their NMR and HRMS<sup>n</sup> data. The anti-inflammatory effects of the crude extract and isolated compounds were evaluated by measuring the levels of interleukins (IL-1β, IL-2, and IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). The crude extract inhibited the release of all cytokines except IL-1β, which slightly increased in comparison to the LPS control. All the tested compounds suppressed the production of IL-2, GM-CSF, and TNF-α. Whereas compounds <b>1</b>, <b>2</b>, <b>4</b>-<b>8</b>, <b>10</b>-<b>15</b>, <b>17</b>, and <b>18</b> decreased production of IL-6, compounds <b>1</b>, <b>2</b>, <b>4</b>, <b>7</b>, <b>10</b>, <b>13</b>-<b>15</b>, and <b>17</b> inhibited the release of IL-1β. It is worth noting that most of the compounds tested showed a superior reduction in cytokines release compared to the reference drug ibuprofen.